Introduction to Human Embryology 馮琮涵 編

Embryo period: from day 0 to the end of 8 week (all major structures are present)
Fetus period: from 9 week to birth (maturation of organs and body growth)

Position, direction and planes:

anterior –posterior; superior –inferior; cranial –caudal; ventral –dorsal;
sagittal plane, horizontal (transverse) plane, frontal (coronal) plane
size: CRL (crown-rump length)

Human Reproduction; Gametogenesis 馮琮涵 編

A. Meiosis -- halves the number of chromosome and DNA strands in sex cells
Meiosis I: DNA replication, recombination and homologous chromosome separate
 two haploid 2N cells
Meiosis II: no DNA replication, double-stranded chromosome division
 four haploid 1N cells

B. Gametogenesis
Primordial germ cells  gametogenesis (mitosis & meiosis)  gametes (sperm or oocyte)
The process of gametogenesis is called spermatogenesis (male) and oogenesis (female)

C. Spermatogenesis (one cycle about 64 days) begins at puberty (testosterone) in the male
Primordial germ cell  mitosis  spermatogonia
 DNA synthesis  primary spermatocyte  meiosis I  secondary spermatocytes
 meiosis II  spermatids  spermiogenesis  sperms (spermatozoa)
sperm: head (acrosome), midpiece (mitochondria), tail (microtubules)

D. Oogenesis is discontinuous and begins during fetal life in female

Primordial germ cell  mitosis  oogonia
 DNA synthesis  primary oocyte  meiosis I prophase arrest (before puberty)
primary oocyte + single-layered follicle cells  primordial follicle

Puberty: GnRH  FSH & LH  primordial follicle  primary follicle (zona pellucida)
 secondary follicle (antrum)  mature follicle

Day 13 or 14 of menstral cycle: FSH & LH stimulate primary oocyte in mature follicle
 finish meiosis I  secondary oocyte + first polar body
 meiosis II metaphase  ovulation
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 Ovulation, Fertilization and Implantation (1st Week) 馮琮涵 編

A. Ovarian cycle (FSH & LH)

Primordial follicle  primary follicle  secondary follicle  maturing follicle
 ovulation  corpus luteum  corpus albicans
Oocyte + zona pellucida + follicular cells (corona radiata cells)

B. Uterine cycle (estrogen & progesterone)

Menstrual phase  proliferative phase  luteal (secretory) phase

If fertilization occurs: hCG keep the corpus luteum and luteal phase continues

The First Week

A. Fertilization (day 0) –occurs in ampulla of oviduct
Sperm: capacitation (seminal proteins are removed from sperm’ s acrosome) in uterus
acrosome reaction (Ca2+ and ZP3 stimulate enzymes release from acrosome)
oocyte: cortical (zona) reaction & 2nd meiotic division
Pronucleus stage  fusion of pronuclei  zygote

B. Cleavage (day 1-- day 4)

Zygote  two-cell stage  compaction (cell adhesion) morula (with zona pellucida)

Blastocyst formation (day 5) (hatching from zona pellucida)

Inner cell mass  embryoblast … embryo
Outer cell mass  trophoblast … placenta

C. Implantation (about day 6)

trophoblast  cytotrophoblast (inner) & syncytiotrophoblast (outer)
 human chorionic gonadotropin (hCG)
 corpus luteum –progesterone  maitain endometrium of uterus

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Bilaminar Germ Disc (2nd Week)& Uteroplacental Circulation 馮琮涵 編

A. Bilaminar germ disc

Trophoblast  syncytio-trophoblast (outer layer) & cyto-trophoblast (inner layer)
Embryoblast  epiblast & hypoblast (bilaminar germ disc)

B. Amniotic cavity = epiblast + amnioblast

Exocoelomic cavity (primitive yolk sac) = hypoblast + e
xoc
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Fibrin coagulum (coagulation plug)
Extraembr yoni
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C. Extraembryonic mesoderm
Chorionic cavity (extraembryonic coelom) & definitive yolk sac + exocoelomic cysts
Connecting stalk  umbilical cord

D. Uteroplacental Circulation
Syncytiotrophoblast  trophoblastic lacunae
Primary stem villus (11-13 days)  secondary stem villus (16 days)
 tertiary stem villus (21 days)
Syncytiotrophoblast + cytotrophoblast + extraembryonic mesoderm (blood vessels)

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 Trilaminar Germ Disc (3rd Week)
& Somite and Neural Tube Development
馮琮涵 編
Outlines: Gastrulation; Formation of Trilaminar Germ Disc;
Initial Development of the Somites and Neural Tube

A. Gastrulation: the process by which bilaminar disc is converted into trilaminar disc
Primitive streak: primitive pit, node and groove
–epiblast migrate to form mesoderm and endoderm (some displace hypoblast)
Buccopharyngeal membrane oral cavity；cloacal memebrane  anus opening
= ectoderm + endoderm (no mesoderm)

B. Notochord formation -- caudal to prechordal plate (mesoderm)): Primitive node

 notochordal process (a mesodermal tube)  fuse with endoderm
 notochordal plate & neurenteric canal  detach from endoderm
 notochord (a solid cylinder) body & nucleus pulposus of vertebra
Neurenteric canal –temporarily connect amniotic and yolk sac cavities

C. Trilaminar germ disc = ectoderm, mesoderm and endoderm

1. Ectoderm -- (prechordal & notochordal plate induce)

Neural plate  neural fold  neural crest & groove  neural tube
Ectoderm  CNS & PNS & sensory epithelium of eye, ear, nose & epidermis
2. Endoderm
CNS growth  cephalo-caudal folding
Somite growth  lateral folding
Yolk sac  foregut, midgut, hindgut & vitelline duct (yolk stalk) & allantois
Endoderm  GI tract & organs & respiratory tract & thyroid, parathyroid
& tonsil, thymus
3. Mesoderm:
a. Paraxial mesoderm  axial skeleton, part of skeletal muscle
b. Intermediate mesoderm  urinary system and parts of genital system
c. Lateral plate mesoderm  splanchnopleuric mesoderm & somatopleuric mesoderm
i. splanchnopleuric mesoderm  smooth muscle of GI tract
ii. somatopleuric mesoderm  inner lining of body wall, parts of limb and dermis

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 a. Paraxial mesoderm  somitomere (except 1-7 pairs)  somite (base of skull)
1-7 somitomeres  muscles of face, jaw, throat
8,9,10… s omi tomere s 1,2,3… s omi t
es
1,2,3,4 somites  occipital part of skull, bones around nose, eyes, inner ears
& muscles of eye ball and tongue
next eight (5-12) somites  8 cervical somites
next twelve (12-23) somites  12 thoracic somites
five lumbar, five sacral and three coccygeal somites

D. Differentiation of Somite
Somites or somitomeres  dermo-myotome (dermatome + myotome) & sclerotome
1. Dermatome  dermis2. Myotome  skeletal muscles3. Sclerotome 
mesenchyme  skeleton

E. Neurulation: formation of neural tube

Ectoderm -- (prechordal & notochordal plate induce)
Neural plate  neural fold  neural crest & groove  neural tube
Ectoderm  CNS & PNS & sensory epithelium of eye, ear, nose & epidermis
F. Development of the intraembryonic coelom
intraembryonic coelom: space between splanchnopleuric & somatopleuric mesoderm

G. Early development of the cardiovascular system

1. angiogenesis: blood vessel formation (angioblast  endothelial cell)
begin in extraembyonic mesoderm of the yolk sac, connecting stalk & chorion
2. hematogenesis: blood cell formation (hemangioblast  blood cell)
begin in the liver, spleen, bone marrow, and lymph node
3. heart and great vessels from mesenchymal cells in the cardiogenic area
paired endocardial heart tubes fuse and form a primordial heart tube
begin to beat on day 21 or 22

H. Development of chorionic villi

Primary stem villus (11-13 days)
 secondary stem villus (16 days)
 tertiary stem villus (21 days)
Syncytiotrophoblast + cytotrophoblast + extraembryonic mesoderm (blood vessels)

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 Embryonic Folding 馮琮涵 編

Outlines: folding of the embryo;

formation of body cavities and mesenteries

Folding –a flat trilaminar germ disc → a three dimentional (3-D) embryo.

Grow faster in length than in width
Length: development of notochord, neural tube & somites
Width: growth of lateral plate mesoderm

A. Cephalic folding
Overgrowth and flexure of cephalic neural plate
1. Mesenchyme (a loose embryonic tissue)
2. Cardiogenic area (cranial to buccopharyngeal membrane) … heart
3. Septum transversum (day 22 –a thicken bar of mesoderm)
… part of diaphragm, ventral mesentery of stomach and duodenum

B. Caudal folding
Overgrowth and flexure of neural tube and somites
1. Cloacal membrane → ventral surface
2. Connecting stalk (connect caudal end of germ disc to placenta)
→ merges with the neck of yolk sac
3. Allantois: a endodermal hindgut diverticulum

C. Lateral folding
Overgrowth and flexure of lateral plate mesoderm
1. Lateral edges of germ disc fuse along ventral midline except umbilical region
2. Umbilical region: yolk sac + connecting stalk

D. Folding of endoderm → gut tube

Foregut, midgut, hindgut, allantois and vitelline duct (neck of yolk sac)

E. Intraembryonic coelom -- lateral plate mesoderm splits into two layers:

1. Somato-pleuric (somatic) mesoderm (adheres to ectoderm)
→ serous membrane of inside of body wall
2. Splanchno-pleuric (visceral) mesoderm (adheres to endoderm)
→ serous membrane of visceral organs and gut tube

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F. Mesenteries:
1. ventral mesentery: from septum transersum
2. dorsal mesentery: bilayered splanchno-pleuric mesoderm

a. intraperitoneal organs: suspended in peritoneal cavity

b. retroperitoneal organs: behind the peritoneum ex. kidneys and urinary bladder
c. secondarily retroperitoneal organs: initially suspended by mesentery →
fused to body wall ex. duodenum, pancreas, ascending colon and descending colon

G. Ventral body cavities

1. Septum transversum (4th week)
a. Primitive pericardial cavity (superior)
b. Peritoneal cavity (inferior)
i. Pericardio-peritoneal canals
ii. Phrenic nerve (C3, C4, C5) elongation

2. Pleuro-pericardial folds (5th week) divide primitive pericardial cavity into

a. Difinitive pericardial cavity
b. Pleural cavities (two)

Pleuro-pericardial folds: three layer:

Outer somatic mesoderm → mediastinal pleura
Body wall mesenchyme → fibrous pericardium (with phrenic nerves)
Inner somatic mesoderm → parietal pericardium

3. Pleuro-peritoneal membranes –seal off pericardio-peritoneal canals (7th week)

Left canal is larger and close later than right canal

H. The diaphragm
1. septum transversum → central tendon of diaphragm
2. pleuro-peritoneal membranes → the bulk of diaphragm muscle
3. body wall mesoderm → outer rim of diaphragm muscle
4. esophageal mesoderm → right and left crura of diaphragm

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 The muscular system 邱瑞珍 編

A. General description
1. Muscular system from mesoderm, iris from neuroectoderm
2. Myoblast:
a. embryonic muscle cells from mesenchyme
b. head: much from neural crest
pharyngeal arches formed musculature of head & neck

B. Development of skeletal muscle

1. Derived from mesoderm in the myotome region of the somite
2. Limb muscles from myogenic precursor cells in limb buds
3. First indication of myogenesis:
a. mesenchymal cells elongation of the nuclei & cell bodies
b. form myoblasts
c. fuse of myobast
d. form elongated, multinucleated, cylindrical myotube
4. Muscle growth from fusion of myoblasts & myotube
a. myofilaments develop during or after fusion
b. then myofibril, organelles develop
5. Striated muscle cells long & narrow called muscle fibers
6. Myotube differentiated and invested by external lamina
7. Fibroblast produce perimysium & epimysium
8. Endomysium derived from external lamina from muscle fiber & reticular fibers
9. Most muscle develop before birth and almost remaining formed by the end of first year
10. After first year increasing in size:
a. increase diameter of muscle fibers
b. formation of more myofilaments
11. Increase in length & width grow with skeleton

C. Myotomes
1. Each myotome:
a. dorsal –epaxial division
b. ventral –hypaxial division
2. Spinal nerve:
a. dorsal primary ramus supply epaxial division
b. ventral primary ramus suppy hypaxial division
c. Some (intercostal): remain segmentally arranged
d. others: migrate to other place and not segmentally arranged
3. Derivatives of epaxial division of myotome
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 a. Segmental muscles of main body axis
b. Extensor muscle of neck & vertebral column
c. extensor from sacral & coccygeal myotomes degenerated
adult decome dorsal sacrococcygeal ligament
4. Derivatives of hypaxial divisions of myotomes
a. Cervical myotome become scalene, prevertebral, geniohyoid, infrahyoid muscles
b. Thoracic myotome become lateral & ventral flexor muscles of vertebral column
c. Lumbar myotome become quadratus lumborum muscle
d. Also formed muscles of limbs, intercostal muscles, abdominal muscles
e. Sacrococcygeal myotomes become muscles of pelvic diaphragm, anus & sex organs
5. Pharyngeal arch muscle
Muscles of mastication, facial expression, pharynx, larynx
6. Ocular muscles
a. From mesenchymal cells near prechordal plate
b. Mesoderm become 3 preoptic myotomes:
supply by its own cranial nerve CN III, CN IV, CN VI
7. Tongue muscle
a. Initially: 4 occipital (postotic) myotomes
b. first disappear
c. remaining become tongue muscles: innervated by CN XII
8. Limb muscles
a. From myoblast surrounding bones
b. Originate from somite
c. First located in ventral part of dermomyotome: epithelial in nature
d. Cells migrate become primordium of limb

D. Development of smooth muscle

1. From splanchnic mesenchyme surrounding primordial gut
2. In walls of blood & lymphatic vessels from somatic mesoderm
3. Muscles of iris, myoepithelial cells in mammary & sweat gland from ectoderm
4. First sign:
a. elongated nuclei in spindle-shaped myoblasts
b. do not fuse
c. Early: mesenchymal cells become myoblasts
d. Later: myoblasts become smooth muscle cells

E. Development of cardiac muscle

1. From lateral splanchnic mesoderm surrounding heart tube become cardiac myoblasts
2. Recognizable: in 4th week
3. Myoblast adhere but intervening membrane still become intercalated discs
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4. Late in embryonic period:
a. cells: few myofibrils, larger diameter become Purkinje fibers
b. form conducting system of the heart

F. Development of the diaphragm

1. Dome-shaped, musculotendinous, Separate thoracic &abdominal cavities
2. Develops from:
a. septum transversum
b. pleuroperitoneal membranes
c. dorsal mesentery of esophagus
d. lateral body walls
3. Septum transversum
a. Mesodermal tissue
b. Primordium of the central tendon
c. Grows from ventrolateral body wall
d. Semicircular shelf between heart-liver
e. Early develop when liver embedded in
f. Caudal to pericardial cavity
g. First identifiable at end of 3rd week: cranial to pericardial cavity
i. Head folds ventrally: between pericardial cavity and abdominal cavities
ii. formed large opening: pericardioperitoneal canal on each side of esophagus
iii. Septum transversum gorws into dorsal mesentery of esophagus & pleuroperitoneal
membranes
4. Pleuroperitoneal membranes
a. Fuse with dorsal mesentery of esophagus & septum transversum
b. Completes partition between thoracic and abdominal cavities
primordial diaphragm
c. Fetal: large portion
d. Newborn: small parts
5. Mesentery of esophagus
a. After fusion: become median portion of diaphragm
b. Crura of the diaphragm derived from myoblast gorws into mesentery
6. Muscular ingrowth from body wall
a. 9th-12th weeks: lung & pleural cavities enlarge invade lateral body walls
b. Body tissue:
i. external layer: become part of abdominal wall
ii. internal layer: become peripheral portions of diaphragm, external to pleuroperitoneal
membranes
c. Extension of pleural cavities form costodiaphragmatic recesses
cause dome-shaped of diaphragm
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7. Positional changes & innervation of the diaphragm
a. 4th week: septum transversum at 3-5 cervical somites
b. 5th week: myoblast grows in developing diaphragm bring nerve fiber
c. Phrenic nerve from ventral primary rami: C3-5
d. Rapid growth of dorsal part: apparent descent of diaphragm
e. 6th week: at thoracic somites
f. 8th week: at 1st level of lumbar vertebrae
g. Phrenic nerve: lengthening with diaphragm position
h. 4 parts of diaphragm fuse: mesenchyme in septum transversum transfer to other 3 parts
forms myoblasts become skeletal muscle
i. Motor innervation: phrenic nerve, Sensory innervation: phrenic nerve
j. costal rim: intercostal nerve (origin from lateral body walls)

G. Early stages of limb development

1. Limb buds: small elevations of ventrolateral body wall
2. Upper limb buds: day 26 or 27
3. Lower limb buds: a day or 2 days later
4. Each limb bud: mesenchyme cover by ectoderm
5. Mesenchyme: from somatic layer of lateral mesoderm
6. Limb elongation: mesenchyme proliferation
7. Upper & lower limbs: alike
a. upper 2 days precedes
b. upper: caudal cervical segments
c. lower: lumbar & upper sacral segmetns
8. Apex of limb buds: ectoderm thickens
a. apical ectodermal ridge (AER): multilayer epithelial structure
b. promote outgrowth of bud
c. initiates growth: proximodistal axis
9. Mesenchymal cells aggregate in posterior margin of limb buds formed zone of polarizing activity
(ZPA)
a. Fibroblast growth factor (from AER) activates ZPA
b. expression sonic hedgehog gene (Shh)
c. control patterning of limb along anteroposterior axis
d. Wnt7(dorsal) & En-1(ventral): specifying dorsoventral axis
10. Distal end: paddle-like hand & foot plates
a. End of 6th week: hand plates become digital rays
b. 7th week: foot plates become digital rays
c. At tip of digital rays: AER induce development of phalanges
d. Intervening regions: breakdown to form notches between digital rays
e. End of 8th week: separate digits formed
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 f. Programmed cells death response for tissue break down

H. Final stages of limb development

1. 5th week: mesenchymal model of bone develop chondrification centers
2. End of 6th week: limb become cartilaginous
3. 7th week: osteogenesis of long bone
4. carpal bone ossification : during 1st year
5. as long bone form: myoblast aggregate form muscle mass
a. Dorsal: extensor
b. Ventral: flexor
6. Mesenchyme in limb bud give rises to bones, ligaments, blood vessels
7. myogenic precursor cell migrate to limb buds later differentiate into myoblasts
8. Cervical myotomes contribute to muscles of pectoral girdle
9. Lumbosacral myotomes contribute to muscles of pelvic girdle
10. Early in 7th week: limbs extend ventrally
11. Limb rotates:
a. Upper limb: rotate laterally 90 degree
b. Lower limb: rotate medially almost 90 degree

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 The cardiovascular system 邱瑞珍 編

Cardiovascular system: the first major system to function in embryo

Primordial heart & vascular system: appear in the middle of 3rd week
Heart start to function: beginning of 4th week
Rapidly growing embryo: nutrient & oxygen not satisfy by diffusion

A. Early development of the heart & vessels

1. Earliest sign: paired endothelial strands: angioblastic cords
In cardiogenic mesoderm –during 3rd week
2. Angioblastic cords
a. Canalize
b. Formation of heart tubes
c. Fuse  tubular heart –late 3rd week
3. Anterior endoderm: inductive influence to stimulate early formation of heart
4. Cardiac morphogenesis: controlled by cascade of regulatory genes & transcription factors

B. Development of the veins associated with the heart

1. 3 paired veins enter tubular heart (4-week embryo)
a. Vitelline veins: return poorly: oxygenated blood from yolk sac
b. Umbilical veins: carry well-oxygenated blood from chorion
c. Common cardinal veins: return poorly oxygenated blood from the body of embryo
2. Passing septum transversum: Vitelline veins enter venous end of the heart - sinus venous
3. Liver primordium grows into septum transversum:
a. Hepatic cords : anastomose around pre-existing endothelium spaces
b. Spaces: primordia of hepatic sinusoids linked to vitelline veins
4. Hepatic veins: form from R. vitelline veins
5. Portal veins: from an anastomotic network of vitelline veins –around duodenum
6. Fate of umbilical veins:
a. R. Umbilical vein & proximal part of L. umbilical vein (Between liver & sinus venosus):
degenerate
b. Caudal part of L. umbilical vein becomes umbilical vein:
carry well-oxygenated blood from placenta to embryo
c. Venous shunt: ductus venous (develop within liver)
i. Connects: umbilical vein & inf. vena cava
ii. Bypass liver: blood directly to heart
7. Cardinal veins: main venous drainage system of embryo
a. Anterior: drain cranial part
b. Posterior: drain caudal part
c. Both  Common cardinal vein enter sinus venosus
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 d. During 8th week:
i. Anterior cardinal veins: connected formed oblique anastomosis
ii. Blood: from right to left become L. brachiocephatic vein
iii. Caudal part of L. degenerate
e. Superior vena cava: from R. anterior cardinal vein & common cardinal vein
f. Posterior cardinal: in adult: become root of azygos vein & common iliac vein
g. Subcardinal & supracardinal veins: replace posterior cardinal vein
h. Subcardinal appear first: form stem of L. renal v., suprarenal v., gonadal v., segment of inf.
vena cava
i. Supracardinal veins: disrupted in the renal region
1) Cranial: become azygos & hemizygos veins
2) Caudal: left –degenerate, right become inferior part of inferior vena cava
8. Inferior vena cava: blood returning from the caudal part of embryo
a. Shifted: left to right
b. Composed 4 main segments:
i. Hepatic segment: from hepatic vein & sinusoids
ii. Prerenal segment: from R. subcardinal vein
iii. Renal segment: sub-supra anastomosis
iv. Postrenal segment: R. supracardinal vein

C. The aortic arches and other branches of dorsal aorta

1. Pharyngeal arches: form during 4th & 5th week
Supply by aortic arches
2. Aortic arches: From aortic sac, terminate: dorsal aortae
Initially: paired dorsal aortae become single-caudal to pharyngeal arches
3. Intersegmental arteries
a. Branches of dorsal aorta: 30
b. Intersegmental arteries to somites & derivatives
c. Dorsal intersegmental arteries in neck join become vertebral arteries
d. Most: disappear
e. In thorax: become intercostal a.
f. In abdomen: become lumbar a.
g. 5th lumbar intersegmental a. become common iliac a.
h. In sacral region: become lateral sacral arteries
i. Caudal end of dorsal aorta: become median sacral artery

D. Fate of vitelline & umbilical arteries

1. Ventral branches of dorsal aorta: supply yolk sac, allantois & chorion
2. Vitelline arteries: to yolk sac & primordial gut
3. 3 vitelline arteries remain:
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 a. Celiac trunk to foregut
b. Superior mesenteric a. to midgut
c. Inferior mesenteric a. to hindgut
4. Umbilical arteries: pass connecting stalk (umbilical cord) become vessels in chorion
a. Carry poorly oxygenated blood to placenta
b. Proximal part: become internal iliac arteries & superior vesical arteries
c. Distal part: obliterated after birth become medial umbilical ligaments

E. Further development of heart

1. Embryonic folding: heart tubes approach each other fuse to become single tube
2. Heart tube fuse:
a. Primordial myocardium: from splanchnic mesoderm-Surrounding pericardial coelom
b. At this stage: Heart composed thin endothelial tube, cardiac jelly, muscular tube
c. Endothelial tube become endocardium
d. Primordial myocardium become myocardium
e. Epicardium: from mesothelial cells from external surface of sinus venosus
3. Folding of head region: Heart & pericardial cavity become ventral to foregut caudal to
oropharyngeal membrane
4. Tubular heart elongated, alternate dilations & constrictions:
truncus arteriosus, bulbus cordis, ventricle, atrium, sinus venosus
a. Tubular truncus arteriosus: cranial to aortic sac
b. Sinus venosus: receives umbilical, vitelline & common cardinal veins
(From chorion, yolk sac, and embryo)
5. Arterial & venous ends of heart: fixed by pharyngeal arches & septum transversum
6. Bulbus cordis & ventricle: grow faster
a. Heart bends become U-shaped: bulboventricular loop
b. Primordial heart bends: atrium & sinus venous become dorsal to truncus arteriosus, bulbus
cordis, ventricle
c. At this stage: sinus venous has lateral expansion: right & left horns
7. As heart develops: invaginates into pericardial cavity
8. Heart: initially suspended from dorsal wall
a. Mesentery - dorsal mesocardium
b. Central part of mesentery: degenerate become transverse pericardial sinus
c. At this stage: heart attached only cranial & caudal ends

F. Circulation through primordial heart

1. Blood enters sinus venosus: from
a. Embryo: common cardinal veins
b. Placenta: umbilical veins
c. Yolk sac: vitelline veins
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2. Sinus venosus enter primordial atrium (control by sinuatrial valves)
 Atrioventricular canal  Primordial ventricle
3. Ventricles contraction :
a. Blood  bulbus cordis & truncus arteriosus  aortic sac  arches (in pharyngeal arches)
b. Blood  dorsal aortae: distribution  embryo, yolk sac, placenta
4. Partitioning of atrioventricular canal, primodial atrium & ventricle:
a. Begins: middle of 4th week
b. Completed: end of 5th week

G. Partitioning of atrioventricular canal

1. Endocardial cushions: form on dorsal & ventral walls of canal
a. Invaded by mesenchymal cells
b. Approach each other & fuse
c. Become right & left AV canals: partially separates atrium & ventricle
2. Cushions: as AV valves
3. Endocardial cushions: from matrix related to myocardium

H. Partitioning of primordial atrium

1. Primordial atrium become right & left: Formation of 2 septa
septum primum & septum secundum
2. Septum primum:
a. Thin, crescent-shaped membrane
b. Grows into endocardial cushions
c. From roof of primordial atrium
d. Partially dividing atrium into right, left
e. Septum primum develops: large opening- Interatrial foramen primum:
Between its free edge & endocardial cushions
f. Foramen primum: as a shunt
i. Allow blood (O2) from right to left
ii. Become smaller when septum fuse with endocardial cushion
iii. When primordial AV septum formed: foramen disappear
iv. Before foramen primum disappear: Central part perforation
1) Perforations: coalesce into foramen secundum
2) Ensure a continuous flow from right to left
3. Septum secudum:
a. Crescentic muscular membrane
b. To the right of septum primum
c. From ventraocranial wall
d. Grows during 5th & 6th week
e. Gradually overlaps: foramen secundum
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 f. Incomplete partition: between atria
g. Opening: oval foramen
4. Septum primum:
a. Cranial part: disappears
b. Remaining part: valve of oval foramen
c. Before birth: Oval foramen:
allows blood from right to left, also prevent blood passage in opposite direction
d. After birth: oval foramen closes, valve fuse to septum secundum
e. Interatrial septum become complete partition

I. Changes in sinus venosus

1. Initially sinus venosus:
a. Open into posterior wall of primordial atrium
b. Right & left horns : same size
c. End of 4th week: right larger than left
d. Sinuatrial orifice move to right, open into primordial atrium (adult right atria)
e. Results of left-to-right venous shunt :
i. Left sinual horn in size & importance
ii. Right: enlarges & receives all the blood
1) From head & neck through SVC
2) From placenta & caudal region through IVC
2. Development proceeds:
a. Left become coronary sinus
b. Right: incorporated into wall of right atrium
3. Sinus venosus fuse to right atrium become smooth part of wall of right atrium:
sinus venarum
4. Remainder of wall of right atrium: rough, trabeculated appearance & muscular pouch –auricle
5. Smooth part - rough part: crista terminalis or terminal crest
Externally: sulcus terminalis or terminal groove
6. Crista terminalis:
a. Cranial part of right sinuatrial valve
b. Caudal part: valves of IVC & coronary sinus
7. Left sinuatrial valve: fuse to septum secundum become interatrial septum

J. Primordial pulmonary vein & formation of left atrium

1. Most wall of left atrium: smooth
formed by : incorporated of primordial pulmonary vein.
2. Vein develop: outgrowth of dorsal atrial wall
3. Atrium expands: veins & branches gradually incorporated into wall of atrium
4. Incorporate into atrium wall: 4 pulmonary veins formed
17
5. Left auricle:
a. Primordial atrium
b. Internal: rough

H. Partitioning of primordial ventricle

1. First indicated: median muscular ridge
a. Primordial interventricular (IV) septum in floor of ventricle
b. Concave edge
c. Increase height: dilation of ventricle
2. Medial wall of ventricle:
a. Approach each other & fuse become primordium of muscular part of IV septum
b. Later: proliferation of myoblasts then increase size
3. 7th week:
a. Crescent-shaped IV foramen between free edge of IV septum & fused endocardial cushions
b. IV foramen usually closed: end of 7th week
c. Bulbar ridges fuse to endocardial cushion
4. Closure of IV foramen & formation of membranous part of IV septum:
From fusion of tissues:
a. Right bulbar ridge
b. Left bulbar ridge
c. Endocardial cushion
5. Membranous part of IV septum: tissue extension
a. From right side of endocardial cushion
b. To muscular part of IV septum
c. Tissue merges to aorticopulmonary septum & thick muscular part of IV septum
6. After closure of IV septum & formation of membranous part :
a. Pulmonary trunk: communicate R. ventricle
b. Aorta: communicate L. ventricle
7. Cavitation of ventricles: spongelike mass of muscular bundles
a. Trabeculae carneae
b. Papillary muscles & tendinous cords

I. Partitioning of bulbus cordis & truncus arteriosus

1. 5th week:
a. Mesenchymal cells in walls of bulbus cordis: active proliferation
formed bulbar ridges
b. Similar ridges also in truncus arteriosus
c. Continuous with bulbar ridges
2. Bulbar & truncal rides: From neural crest mesenchyme
a. Neural crest cells migrate
18
 b. Through primordial pharynx & pharyngeal arches
3. Bulbar ridges continuous with truncal ridges: undergo 180° spiraling
a. Spiral orientation: possibly caused by streaming of blood from ventricles
b. When ridges fuse: form spiral aorticopulmonary septum
4. Aorticopulmonary septum: divides bulbus cordis & truncus arteriosus into 2 arterial channels
a. Aorta
b. Pulmonary trunk
c. Because pf spiraling: pulmonary trunk twists around ascending aorta
5. Bulbus cordis incorporated into walls of ventricles in several ways:
a. In right ventricle:
i. Represented by conus arteriosus
ii. Give origin to pulmonary trunk
b. In left ventricle:
i. Forms walls of aortic vestibule
ii. Part of ventricular cavity just inferior to aortic valve

J. Development of cardiac valves

1. Semilunar valves:
a. From 3 swellings of subendocardial tissue
b. Around orifice of pulmonary trunk & aorta
c. These swellings become hollowed out
i. Reshaped
ii. 3 thin-walled cusps
2. AV valves: develop similarly
localized proliferations of tissue

K. Conducting system of heart

1. Initially: muscles layers in atrium & ventricle continuous
2. Primordial atrium: pacemaker of heart
soon: sinus venosus takes over
3. SA node: develops during 5th week located: right atrium near entrance of SVC
4. After incorporation of sinus venosus:
cells from its left wall: found in the base of interarterial septum
5. Cells from AV region:
a. Form AV node & bundle
b. Located superior to endocardial cushion
6. Fibers from AV bundle:
a. Pass to ventricles
b. Split into right & left bundle branches
7. SA node, AV node, AV bundle: rich supply by nerves
19
8. Primordial conductive system: developed before nerve enter

L. Aortic arch derivatives

1. 4th week: pharyngeal arch supplied by aortic arches
a. From aortic sac
b. In other mammals =ventral aorta
2. Aortic arches terminate in dorsal aorta
a. 6 pairs of aortic arches not all present at the same time
b. 6th pair formed: first 2 disappeared
3. Derivatives of 1st pair of aortic arches
a. Largely disappears
b. Remnants: form parts of maxillary arteries supply ears, teeth, muscles
c. Part of external carotid arteries
4. Derivatives of 2nd pair of aortic arches
a. Dorsal parts: persist
b. Form stems of stapedial arteries: run through ring of stapes
5. Derivatives of 3rd pair of aortic arches
a. Proximal part: form common carotid arteries supply head
b. Distal part: join dorsal aortae formed internal carotid arteries supply ears, orbits, brain &
memninges
6. Derivatives of 4th pair of aortic arches
a. Left: form part of aortic arch
i. Proximal part of arch: from aortic sac
ii. Distal part: from left dorsal aorta
b. Right: becomes proximal part of right subclavian artery
7. Left subclavian a. not from aorta arch
a. From left 7th intersegmental artery
b. Growth shift origin cranially
c. Close to origin left common carotid artery
8. Fate of 5th pair of aortic arches
a. In 50% embryos: rudimentary soon degenerate
b. In others: not develop
9. Derivatives of 6th pair of aortic arch
a. Left 6th aortic arch
i. Proximal part: proximal part of left pulmonary artery
ii. Distal part: pass from left pulmonary artery to dorsal aorta to form prenatal shunt -
ductus arteriosus (DA)
b. Right 6th aortic arch
i. Proximal part: proximal pulmonary artery
ii. Distal part: degenerate
20
10 Transformation of 6th pair of aortic arches: recurrent laryngeal nerves differ on 2 sides
a. Recurrent laryngeal nerves: supply 6th pair pharyngeal arches
b. Hook around 6th pair of aortic arch
c. On the right:
i. Distal part degenerate
ii. Right recurrent laryngeal nerve move superiorly hook around proximal part of right
subclavian artery
c. On the left: Left recurrent laryngeal nerve hook around DA
d. After birth:
i. DA become ligamentum arteriosum
ii. Nerve hook around ligamentum arteriosum

M. Fetal & neonatal circulation

1. Fetal circulation: serve prenatal needs & modifications at birth
2. Prenatally:
a. Lung: does not provide gas exchange
b. Pulmonary vessels constricted
c. 3 shunts allow transitional circulation
i. Ductus venosus
ii. Oval foramen
iii. Ductus arteriorsus
3. Fetal circulation:
a. Umbilical vein transport highly oxygenated, nutrient-rich blood returns from placenta
b. Half of blood  Ductus venosus (DV)  IVC
c. The other half  Hepatic sinusoids  Hepatic vein  IVC
4. Blood flow  DV: Regulate by sphincter mechanism close to umbilical vein
5. After IVC: Blood  R. atrium
a. Most blood: Through oval foramen  L. atrium
b. Blood mix from lung
5. Fetal lung: extract oxygen not provide oxygen
6. From L. atrium: blood  ventricle  Aorta
7. Heart, head, neck, upper limbs, liver: receive oxygenated blood
8. Small amount blood from IVC: remains in R. atrium
a. Mix blood from SVC, coronary sinus (poor oxygen)  R. ventricle (medium oxygenated)
 pulmonary trunk
b. 10% blood  lung
c. Most  DA  aorta  fetal body umbilical artery  placenta
9. High resistance in pulmonary vascular:
a. Flow: low
b. Only small amount blood from ascending aorta  descending aorta
21
 c. 65% descending aorta  placenta
d. 35%  viscera & inferior body

N. Transitional neonatal circulation

1. Circulatory adjustment at birth
a. Blood no longer through placenta
b. Infant’slung s
:e xpa nd&be gi nt
ofunc ti
on
2. As soon as baby is born:
oval foramen, DA, DV, umbilical vessels : no longer needed
3. Sphincter in DV constricts:
all blood  liver through hepatic sinusoids
4. Occlusion of placental circulation:
IVC, R. atrium: blood pressure
5. Increased pulmonary blood flow
a. Pressure: L. atrium > R.
press valve against septum secudum: Closes oval foramen
b. Output from R. atrium: flows entirely into pulmonary circulation
c. Pulmonary vascular resistance < systemic
a. Blood flow in DA : reverse
b. Passing from aorta to pulmonary trunk
6. DA constricts at birth: but for a few days
a. Often: blood from aorta to pulmonary trunk
b. Oxygen: most important factor in DA closure
7. Umbilical arteries constrict at birth: preventing blood loss
8. The change from fetal to adult: not a sudden occurrence
a. Some: occur with 1st breath
b. Some: hours & days
9. During transitional stage:
Right to left flow may occur at oval foramen
10. Closure of fetal vessels, oval foramen:
a. Initially a functional change
b. Later: anatomical closure
proliferation of endothelial & fibrous tissues

O. Adult derivatives of fetal vascular structures

1. Because change in cardiovascular system:
certain vessels & structure no longer required
2. Umbilical vein & ligamentum teres
a. Intra-abdominal part become round ligament of liver from umbilicus to liver
b. Umbilical veins: transfusions
22
3. Ductus venosus & ligamentum venosum
a. DV become ligamentum venosum
b. Closure more prolong than DA
c. From left portal vein to IVC
4. Umbilical arteries & abdominal ligaments
a. Intra-abdominal parts become medial umbilical ligaments
b. Proximal parts become superior vesical arteries supply urinary bladder
5. Ductus arteriosus & ligamentum arteriosum
a. Functional closure: 10-15 hours after birth
b. Anatomical closure & formation of ligamentum arteriosum: 12th postnatal week

P. Development of lymphatic system

1. Develop at end of 6th week
2. Lymphatic vessels: similar to blood vessels
make connection to venous system
3. Early lymphatic capillaries: join together to form network
4. At the end of embryonic period: 6 lymphatic sacs developed
a. 2 jugular lymph sacs: near junction of subclavian veins-anterior cardinal veins
b. 2 iliac lymph sacs: near junction of iliac veins-posterior cardinal veins
c. 1 retroperitoneal lymph sac: at root of mesentery (posterior abdominal wall)
d. 1 chyle cistern: dorsal to retroperitoneal lymph sac
5. Lymphatic vessels: soon join lymph sacs & accompany veins
a. To head, neck, upper limb: from jugular lymph sacs
b. To lower trunk & lower limbs: from iliac lymph sacs
c. To primodial gut: from retroperitoneal lymph sac & chyle cistern
d. 2 large channels (R. & L. thoracic ducts): connect jugular lymph sacs-chyle cistern
e. Soon: anastomosis occurs
6. Thoracic duct develops from
a. Caudal part of R. thoracic duct
b. Anastomosis between thoracic ducts & cranial part of L. thoracic duct
7. R. Lymphatic duct derived from cranial part of R. thoracic duct
8. Enter venosus system at venous angle between internal jugular v. and subclavian v.
9. Development of lymph nodes
a. Except superior part of chyle cistern: lymph sacs transform into groups of lymph nodes
b. Mesenchymal cells invade lymph sacs: form network of lymphatic channels (primordia of
lymph sinuses)
c. Other mesenchymal cells: formed capsule & connective tissue
d. Lymphocyte:
i. Originally from primordial stem cells in yolk sac
ii. Later from spleen & liver
23
 iii. Eventually enter bone marrow: divide into lymphoblasts
e. Lymphocytes appear in lymph nodes:
i. Before birth: derived from thymus (from 3rd pair of pharyngeal pouches)
ii. Small lymphocytes leave thymus circulate to other lymphoid organs
iii. Later: mesenchymal cells in lymph nodes differentiate into lymphocytes
iv. Lymph nodules not appear until just before or after birth
10. Development of spleen & tonsils
a. Spleen: from aggregation of mesenchymal cells in dorsal mesentery of stomach
b. Palatine tonsils: from 2nd pair of pharyngeal pouches
c. Tubal tonsils: from aggregations of lymph nodules around pharyngeal openings of
pharyngotympanic (auditory) tube
d. Pharyngeal tonsils: from aggregatons of lymph nodules in walls of nasopharynx
e. Lingual tonsils: from aggregations of lymph nodules in root of tongue
f. Lymph nodules also develop in mucosa of respiratory & digestive systems

24
 Development of skeletal system 陳金山 編

A. skeletal system developed from mesoderm and neural crest

B. neural tube  somite
1. sclerotome: ventromedial part forming vertebrae and ribs
2. dermomyotome: dorsolateral part forming myoblasts and dermis
C. Development of vertebral column
1. ventral portion of sclerotome surrounds notochord  vertebral body
2. dorsal portion of sclerotome surrounds neural tube  vertebral arch
3. development of intersegmental vertebrae
-- vertebra lies intersegmentally, and spinal nerve segmentally
4. development of intervertebral disk
a. nucleus pulposus: from notochord
b. annulus fibrosus: from sclerotomal cells
D. Developoment of ribs and sternum
1. ribs developed from costal process
2. endochondral ossification
3. sternum developed from sternal bars
E. Development of cranium
1. neurocranium
a. cartilaginous neurocranium: prechordal, hypophyseal, and parachordal
cartilages
b. membranous neurocranium: suture and fontanelle
2. Viscerocranium
a. cartilaginous viscerocranium: from first two pharyngeal arches
b. membranous viscerocranium: squamous temporal, maxillary, zygomatic
bones and mandible
F. congenital anomalies
1. accessory rib
a. lumbar rib
b. cervical rib: may compress brachial plexus of subclavian artery
2. hemivertebra: produce scoliosis
3. acrania: calvaria absent

25
 Development of nervous system 陳金山 編

A. neural plate  neural fold  neural tube

B. formation of neural tube (neurulation)
1. fusion of neural folds
2. rostral and caudal neuropores at both end
3. wall of neural tube thicken to form brain and spinal cord
4. neural canal  ventricular system of brain and central canal of spinal cord
C. Development of spinal cord
1. ventricular zone: give rise to all neurons and macroglia
2. intermediate zone
3. marginal zone  white matter
4. two plates separated by sulcus limitans
a. alar plate: dorsal horn containing afferent nuclei
b. basal plate: ventral and lateral horns containing efferent nuclei
5. congenital anomalies
a. spina bifida occluta
b. spina bifida cystica: protrusion of spinal cord and/or meninges
i. spina bifida with meningocele: sac contains meninges and CSF
ii. spina bifida with meningomyelocele: spinal cord and/or nerve roots
included in the sac
iii. spina bifida with myeloschisis: spinal cord open and neural folds
failed to fuse

D. Development of brain

1. development of myelencephalon
a. formation of alar and basal plates
b. ependyma and pia of roof plate  choroid plexus
26
 c. cranial nerve nuclei  six column
d. migration of some nuclei to a ventral position
2. development of cerebellum
a. from rhombic lip
b. development of nuclei and cortex
3. development of mesencephalon
-- basic alar and basal plate organization
4. development of diencephalon
a. no basal plate
b. hypothalamic sulcus separating thalamus and hypothalamus
c. sulcus dorsalis separating thalamus from epithalamus
d. epithalamic roof plate  pineal gland
e. development of pituitary gland
-- infundibulum (neuroectoderm) downgrowth ventrally
-- Rathke’s pouch (hypophyseal diverticulum) (oral ectoderm)
upgrowth
-- adenohypophysis derived from oral ectoderm
-- neurohypophysis from neuroectoderm
5. development of telencephalon
a. cerebral hemisphere as outgrowth of telencephalon
b. expansion of hemisphere in all directions
c. rotation into “C”shape
6. congenital anomalies
a. cranium bifidum: defect in formation of cranium
i. cranial meningocele: meninges herniated
ii. meningoencephalocele: herniation of meninges and part of brain
iii. meningohydroencephalocele: protruding brain contains part of
ventricular system
b. microcephaly
-- calvaria and brain are small
-- result of microencephaly
c. hydrocephalus
-- excess CSF
-- blockage of CSF circulation results in dilation of ventricle

E. Development of PNS
1. PNS develops mostly from neural crest
2. sensory cells in ganglion of CN VIII remain bipolar
3. sensory ganglia from neural crest and ectodermal placodes
4. autonomic ganglia from neural crest
27
 呼吸 鄭海倫 編
A. Development of the nasal cavity
1. Nasal (olfactory) placodes invaginate into nasal (olfactory) pits by the 4th week.
2. The medial prominence and the lateral prominence form primordial nasal sac.
3. Oronasal membrance (ruptured at the end of the sixth week) separates the oral cavity
and the nasal sacs.
4. The primordial choanae (lie posterior to the primary palate) are the region of
continuity between the nasal and oral cavities.
5. The ectodermal epithelium in the roof of each nasal cavity becomes specilized to form
the olfactory epithelium.

B. Development of the palate

1. Palatogenesis begins at the end of the 5th week and completed until 12th week.
2. The critical period is from the end of the 6th week until the beginning of the 9th week.
The primary palate (median palatine process)
The secondary palate

C. Development of the larynx

1. The epithelial lining of the larynx develops from the endoderm of the cranial end of
the laryngotracheal tube.
2. The laryngeal cartilages develop from mesenchyme (derived from the neural crest
cells).
3. The laryngeal muscles develop from myoblasts in the 4th and 6th pairs of pharyngeal
arches (innervated by the laryngeal branch of the vagus nerve).

D. Developmental aspects of the bronchi and lungs

1. The tracheal bud develops during the 4th week and divides into two outpouchings
(primary bonchial buds).
2. The respiratory tree originates as a foregut diverticulum (lung bud) appears on day
22.
3. The primary bronchial buds appears on days 26 to 28.
4. The secondary bronchial buds appear on early in the 5th week.
There are 5 secondary bonchial buds.
5. Mucosae of the bronchi and lung alveoli are present by the 8th week.
6. By week 16, teminal bronchioles appear.
7. Between 16 and 28 weeks, the respiratory bronchioles appear.
8. By the 28th week, a baby born prematurely can breathe on its own.
9. During fetal life, the lungs are filled with fluid and blood bypasses the lungs.
10. Gas exchange takes place via the placenta.

28
E. Maturation of the lungs
1. Pseudoglandular period (6-16 weeks)
2. Canalicular period (16-26 weeks)
3. Terminal saccular period (26 weeks to birth): capillaries begin to bulge into the
developing alveoli
Type I and type II alveolar cells appear.
4. Alveolar period (32 weeks to 8 years): each respiratory bronchiole terminates in a
cluster of thin-walled terminal saccules, separated from one another by loose
connective tissue.
5. Characteristic mature alveoli do not form until after birth; about 95% of alveoli
develop postnatally

F . Development of the lung

1. By week 36, the invested network of capillaries are formed (called terminal sacs or
primitive alveoli). Limited respiration is possible at the time.
2. At birth, respiratory centers are activated, alveoli inflate, and lungs begin to
function.
3. After birth additional 7 orders of airway branching still occurs.
4. Respiratory rate is highest in newborns and slows until adulthood.
5. Lungs continue to mature and more alveoli are formed until young adulthood.
6. Respiratory efficiency decreases in old age.

消化 鄭海倫 編
A. Embryonic development of the digestive system
1. At the 3rd week the endoderm has folded and foregut and hindgut have formed.
2. The midgut is open and continuous with the yolk sac.
3. Mouth and anal openings are nearly formed.
4. At the 8th week the accessory organs are budding from endoderm.

B. Organs developed from the abdominal foregut

1. Stomach: rotates during the 7th and 8th weeks around 2 axes (craniocaudal and
ventrodorsal).
2. Duodenum
3. Pancreas: the dorsal and the ventral buds fuse to form the definitive pancreas by the
lately 6th week.
4. Liver
The hepatic plate appears on about day 22.
5. Gallbladder
The cystic diverticulum forms the gallbladder and cystic duct.
29
C. Development of the liver
1. The liver parenchyma, the gallbadder, and their ducts bud from the duodenal
endoderm and grow into the septum transversum.
2. The hepatic plates form a hepatic diverticulum.
3. The hepatic diverticulum gives rise to the liver cords (hepatocytes), the bile
canaliculi, and the hepatic ducts.
4. The mesoblastic supporting stroma, in contrast, develops from splanchnopleuric
mesoderm.
5. The ventral mesentery gives rise to the faciform ligament, the lesser omentum, the
hepatoduodenal ligament and the hepatogastric ligament.

D. Development of the midgut

1. The presumptive ileum and the presumptive colon are distinguished separated by a
cecal primordium.
2. The primary intestinal loop appears and attached to the umbilicus by the vitelline
duct.
3. The cranial limb of the primary intestinal loop gives rise to the ileum, and its caudal
limb becomes the ascending and transverse colons.
4. The herniated primary intestinal loop undergoes an initial 90-degree
counterclockwise rotation (by the early 8th week).
5. The jejunum, cecum and vermiform appendix forms.

E. Development of the hindgut

1. The cloaca is partitioned into a posterior rectum and an anterior primitive
urogenital sinus by the urorectal septum (between 4 and 6 weeks).
2. The urorectal septum fuses with the cloacal membrane (the zone of their fusion
becomes the perineum) and dividing into and anterior urogential membrame and a
posterior anal membrane.

F. Anorectal canal
1. The superior 2/3 of the anorectal canal forms from the distal part of the hindgut.
2. The inferior 1/3 is derived from an ectodermal pit (anal pit or protodeum).
3. The anal membrane breaks down in the 8th week and forms an irregular folding of
mucosa called the pectinate line.

30
 Development of Urinary System 周綉珠 編

A. Source:
Intermediate Mesoderm

Urogenital Ridge
 
Nephrogenic Cord Gonadal Ridge
 
Urinary System Genital System

B. Kidneys and Ureters

Three successive (cranial  caudal) developing kidney types
Pronephros—Mesonephros--Metanephros
1. Pronephros
a. Develops at 4th week
b. Cranial located
c. Consist of:
@cell clusters- rudimentary
@pronephric ducts- persist for mesonephric ducts open into cloaca
d. Non functional
e. Persists until 6th week ---vestigial
2. Mesonephros
a. Develops at end of 4th week
b. Located caudal to the rudimentary pronephroi
c. Consist of:
@mesenchymal cell clusters
 mesonephric vesicle  glomerular capsule + mesonephric tubules
(mesonephric tubules  efferent ductules of testes)
@glomeruli- from dorsal aorta
@mesonephric ducts- from pronephric ducts
--- urinary system- collecting tubules, calices, pelvis and
ureter
--- male genital system- ducts of epididymis, ductus
deferens, ejaculatory duct, seminal vesicle
d. Well developed and function (6th –10th week)
e. Till permanent kidney develop (as embryonic kidney)
# Mesonephric ducts
a. solid long. rods (24 days )dorsolateral to mesonephric tubules
b. caudally grow cells at caudal tips proliferation and migration
31
 c. diverge (day 26) from intermediate mesoderm and to fuse with
cloaca (fusion regionpart of post. wall of urinary bladder)
d. canalization from caudal to cranial---mesonephric ducts formed
e. fuse with mesonephric tubules
3. Metanephros
1. Caudally located
2. Develops early in 5th week
3. 4 weeks later begin to function
4. Consist of:
@ metanephric mass (metanephric blastema)
from caudal part of nephrogenic cord nephrons
@ metanephric diverticulum (ureteric bud)
outgrowth of mesonephric duct near its entrance into
cloaca  ureter + pelvis + calices + collecting duct system
5. Permanent kidneys
4. Reciprocal inductive effects between ureteric bud and metanephric
blastema
a. Inductive signal (GDNF:glia derived neurotrophic factor) from
metanephric blastema
b. Ureteric buds sprout from distal portion of mesonephric ducts
c. Ureteric bud grow into metanephric blastema (5th w) begin to
Bifurcate which lobulated kidney and induce nephrons
differentiation
5. Development of Metanephros
a. Branching of ureteric bud
*renal pelvis: 6th w 1st bifurcation of ureteric bud
*major calyces: collapse the 2nd–5th bifurcation
*major calyces: collapse the 6th –9th bifurcation
*collecting ducts: end portion of continue bifurcates, approximately 11
additional generations, 1-3 millions brs.
b. Develop of metanephric blastema
metanephric blastema tissue cap (induced by collecting duct) 
metanephric vesicle  metanephric tubule  metanephric excretory unit:
@Bowman`s capsule: free end of nephric tubule with a capillary
glomerulus to form renal corpuscle
@renal tubules: Proximal convoluted tubule
Loop of Henle
Distal convoluted tubule
*distal convoluted tubule connect collecting duct become functional
important for the production of amniotic fluid (10th w)
32
 6. Ascent of kidneys (6th -9th W)
from sacral to lumbar
1. Caudal part of embryo growth  ascent of kidneys
2. Move farther apart
3. 90 degrees medial rotation: hilum faces ventrally medially

C. Urinary bladder and Urethra

1. Derived from---
@ Epithelium: endoderm of urogenital sinus
# male urethra:
endoderm of urogenital sinus (most)
surface ectoderm (distal part of urethra--glans)
PS: terminal part of urethra in both male and female both
derived from surface ectoderm
@ CT & smooth muscle:
adjacent splanchnic mesenchyme

2. Urogenital sinus
Differentiates from hindgut -- coloaca (4th W- 6th W)
vesicle part- urinary bladder
pelvic part- pelvic urethra
phallic part- definitive urogenital sinus: distal expansion of
urogenital sinus

3. Urinary bladder
a. Mainly: vesicle part of urogenital sinus
b. Trigone: caudal end of mesonephric duct
sup. part of bladder ----allantois  urachus median umbilical lig.
c. Exstrophy of mesonephric ducts and ureters into bladder wall:
between 4-6 weeks
i. root of mesonephric duct post. wall of developing bladder
ii. openings of ureteric buds  post. wall of developing bladder
iii. openings of mesonephric ducts inferiorly to open into pelvic
(prostatic) urethra
iv. urinary trigone formation

4. Urethra
a. male:
i. pelvic urethra  prostatic urethra, membranous urethra
ii. phallic part  penile urethra
33
 b. female:
pelvic urethra  membranous urethra
PS: phallic part  vestibule of vagina
D. Summary
1. Intermediate mesoderm along the posterior aspect attempts to differentiate 3 times into the
kidneys:
Pronephros  mesonephros  metanephros
2. Metanephos forms the nephrons
3. The ureteric bud forms the duct system
4. Urogenital sinus forms the bladder and urethra

34
 Development of Genital System 周绣珠 編

A. Sourse
Intermediate Mesoderm

Urogenital Ridge
 
Nephrogenic Cord Gonadal Ridge
 
Urinary System Genital System

B. Gonads
1. Sources:
a. Mesothelium: mesodermal epithelium on medial side of mesonephros
b. Mesenchyme: embryonic connective tissue underlying the
Mesodermal epithelium
c. Primordial germ cells: originate from yolk sac

2. Indifferent state or Ambisexual

a. Gonadal ridge formation (5th W)
i. Proliferation of mesothelium and underlying mesenchyme 
gonadal ridge
ii. Mesothelium  finger like epithelial cords (as gonadal cords)
grow into mesenchyme  outer-cortex, inner-medulla
b. Primordial germ cells migration (5th W)
From yolk sac dorsal mesentery gonadal ridge and corporated
into gonadal cords (at T10, 6th W)

3. Sex Determination
a. Sex establish at fertilization:
X-bearing sperm + X-bearing ovum  female
Y-bearing sperm + X-bearing ovum  male
b. Gonadal development:
TDF:Testis-determining factor produced by SRY gene
SRY gene located on short arm of Y chromosome (SRY:
Sex-determing region of Y chromosome)

4. Male Pattern (7th W)

Depends upon SRY gene on Y chromosomeTDF testes
--- cortical sex cords degenerate
35
 medullary sex cords developdeveloping testes  seminiferous
cords  seminiferous tubules, straight tubules and rete testis
@ seminiferous tubules
- primordial sperm cells: primordial germ cells
- sertoli cells: surface epithelium, supporting cells of seminiferous
Tubules, secrete antimullerian hormone (AMH)
@ mesenchyme
- Leydig cells: mesenchymal cells, secrete testosterone &
androstenedione causing mesonephric duct and external
genitalia to developing

5. Female Pattern (10th W)

Absence TDF and testosterone
 not to develop male structures  female development
a. primitive sex (gonadal) cords degenerate
b. secondary sex (cortical) cords development from mesothelium of genital
ridge into underlying mesenchyme
c. secondary sex cords invest primordial germ cells as follicle cells
 primordial follicles (16th w):
i. primordial germ cells  oogonia
ii. a single layer of follicular cells (from surface epithelium)
d. oogonia enter 1st meiotic division as primary oocytes (before birth) which
arrest continuous develop by primordial follicles until puberty

C. Development of Genital Ducts and Glands

1. Development of Male Genital Ducts and Glands
a. Mesonephric ducts
Under influence of testosterone (8th –12th w)
i. mesonephric ducts transform into ductus deferens
ii. cranial end of mesonephric ducts degenerate  appendix
epididymis
iii. region between presumptive testis and vas deferens 
epididymis
iv. region between presumptive testis and epididymis (5-12 sup.
part of mesonephric tubules)  ductuli efferentes (connect
with rete testis)
v. caudal end  seminal vesicle
vi. region between seminal vesicle and urethra  ejaculatory duct
vii. inferior part of mesonephric tubules degenerate paradidymis
viii Mmullerian-inhibiting substance (MIS)  paramesonephric
36
 duct degenerate  appendix testis
b. Male accessory glands (8th-10th W)
i. seminal vesicles—sprout from mesonephric ducts with adjacent
mesenchyme
ejaculatory duct: portion of vas deferens to connect with
seminal vesicle
ii. prostate gland—development from endoderm of prostatic
urethra (glandular epi. ) and adjacent mesenchyme (stroma
and smooth muscle)
@urogenital sinus →Shh and Hox genes → prostate develop
iii. bulbourethral glands—development from endoderm of spongy
urethra (glandular epi. ) and adjacent mesenchyme

2. Development of Female Genital Ducts and Glands

a. Paramesonephric ducts (8th –12th w)
In 6 w embryo, paramesonephric ducts (Mullerian ducts ) are formed on
gonadal ridge from T3 to post. wall of urogenital sinus by thickened
mesothelium epi. which lateral to mesonephric ducts.
No MIS
 oviduct, uterus, and superior vagina
No Testosterone
 mesonephric ducts degenerate  appendix vesculosa, duct of
epoophoron, and duct of Gartner, Gartner`s cysts
 mesonephric tubules degenerate  paroophoron, epoophoron
i. unfused superior part  oviduct, superior opening 
infundibula
ii. distal end fused uterovaginal primordium (3rd M)
 uterus and sup. part of vagina
iii. uterovaginal primordium connect with urogenital sinus
 sinus tubercle (a slight thickening of post. wall of pelvic
urethra--endoderm)
iv. sinus tubercle continues to thicken  sinovaginal bulbs
v. sinovaginal bulbs fuse  vaginal plate
vi. vaginal plate elongates and canalized (by desquamation)  inf.
vaginal lumen
vii. vagina junction with urogenital sinus (endoderm of urogenital
sinus)  mucosa of vagina and cervix
viii. endodermal membrane separates lumen of vagina from
urogenital sinus  hymen present at external os of vagina
b. Female accessory glands (8th-10th W)
37
 i. Urethral glands and paraurethra glands:
grow from urethral into surrounding mesenchyme as prostate
in male
ii. Greater vestibular glands:
outgrowth from urogenital sinus as bulbourethral glands in
male

D. Development of External Genitalia

• External genitals similar before 9th W
• DHT causes external male structures to develop before birth
– Genital tubercle: glans penis or clitoris
– Labioscrotal swelling: scrotum or labia majora
– Urogenital folds: spongy penile urethra or labia minora
• Absence of DHT results in development of female
1. Indifferent stage (4th -7th w) :
a. cloacal folds develop on either side of cloacal membrane ante. connect
cloacal folds genital tubercle
b. labioscrotal swelling appear on either side of cloaca folds
c. urorectal septum fuse cloacal membrane  perineum(central tendon)
d. cloacal folds ante. to perineum  urogenital folds  urogenital
groove (endoderm) post. to perineum  anal folds
e. cloacal membrane ante. to perineum  urogenital membrane
post. to perineum  anal membrane
f. urogenital membrane ruptures (7th W)  urogenital orifice
i. genital tubercle elongates  primordial phallus
ii. coronary sulcus demarcated primordium of glans clitoris and
glans penis from phallic shaft

2. Male external genitalia (9th-12th W)

a. effects by testosterone
b. phallus enlarges and elongates long & broad
c. urethral groove becomes solid (proliferation of endoderm)
 urethral plate  recanalizes  (spongy urethra)
d. labioscrotal and urogenital folds fuse scrotal raphe and penile
raphe
e. genital tubercle glans and shaft of penis
f. urogenital fold  penis surrounding spongy urethra
g. labioscrotal fold  scrotum
h. an ectodermal ingrowth at tip of glans  ectodermal cord
i. ectodermal cord canalized to meet spongy urethra full male
38
 urethra
j. a circular ingrowth of ectoderm at periphery of glans break down
 prepuce
k. corpus spongiosum and corpora cavernosa develop from phallic
mesenchyme

3. Female external genitalia (9th-12th W)

1. absence of testosterone, and estrogens involved
2. phallus and urogenital groove not lengthen  shorter & tapered
3. labioscrotal and urogenital folds do not complete fused
4. genital tubercle---glans and shaft of clitoris
5. phallic part of urogenital sinus---vestibule of vagina
6. urogenital fold---labia minor
fused post. frenulum of labia minora
7. labioscrotal fold---labia major
fused ante. ante. labial commissure and mons pubis
fused post.  post. labial commissure

E. Vestigial structures derived from embryonic genital ducts

Male Embryonic Female

testes Indifferent gonad ovary

Seminiferous tubules Cortex Ovarian follicles

Rete testis Medulla Rete ovarii

gurbernaculum Gurbernaculum Ovarian lig.

Round lig. of uterus

Efferent ductules of testis Mesonephric tubules Epoophoron

paradidymis Paroophoron

Appendix of epididymis Mesonephric duct Appendix vesiculosa

Duct of epididymis Duct of epoophoron
Ductus deferens Duct of Gartner
Ureter, pelvis, calices and Ureter, pelvis, calices and
collecting tubules collecting tubules
Ejaculatory duct and

39
 seminal gland

Appendix of testis Paramesonephric duct Hydatid (of Morgagni)

Uterine tube
Uterus
Vagina (sup.)
Urinary bladder Urogenital sinus Urinary bladder
Urethra (except navicular Urethra
fossa) Vagina (inf.)
Prostatic utricle Urethral and paraurethral
Prostate glands
Bulbourethral glands Greater vestibular glands
Seminal colliculus Sinus tubercle Hymen

Penis Phallus Clitoris

glans of penis glans of clitoris
corpora cavernosa of corpora cavernosa
penis of clitoris
corpus spongiosum bulb of vestibule
of penis
Ventral aspect of penis Urogenital folds Labia minora

Scrotum Labioscrotal swellings Labia majora

F. Development of Inguinal Canals

Pathway for testes to descend into scrotum, develop in both sexes
@Gubernaculum: a ligament (condensed subserous fascia)
 descends from inferior pole of gonad
 passes obliquely through developing ante. abd wall
 future inguinal canal
 internal surface of labioscrotal swellings
@Processus vaginalis: envagination of peritoneum
 ventral to inferior root of gubernaculum
 herniates through the abd. wall along the path formed by gubernaculum
# Processus vaginalis carries extensions of layers of abd. wall before it 
Coverings of spermatic cord and testis
1. Descend of Testes ( from T10 level, 7th M)
40
 a. associated with:
i. enlargement of testes
ii. atrophy of mesonephroi
iii. atrophy of paramesonephric ducts (induced by MIS)
iv. enlargement of processus vaginalis
b. controlled by androgens and guided by processus vaginalis
c. takes 2-3 days (through inguinal canals into scrotum at 26th w)
d. carries with it the ductus deferens and associated blood vessels and
fascia
e. coverings of spermatic cal and testis
i. transversalis fascia (deep ring) internal spermatic fascia
ii. muscle fibers and fascia of internal oblique muscle 
cremasteric fascia
iii. external oblique muscle (superficial ring)  external spermatic
fascia

2. Descend of Ovaries ( from T10 level, 7th M)

gubernaculums attached to developing paramesonephric ducts
 ovaries suspended in broad ligament of uterus
superior gubernaculums  ovary ligament
inferior gubernaculums  round ligament of uterus

G. Summary
• Three weeks later than urinary system
• Gonads develops from:
1. Primordial germ cells
2. Mesothelium
3. Mesenchyme
• Genetic sex is established at fertilization
• TDF(SRY gene) directs testicular differentiation
• External genitalia from:
1. Labioscrotal swelling
2. Urethral folds
3. Genital tubercle

41
 Development of Endocrine 柯翠玲 編

A Pineal gland
1 The epithalamus  roof and dorsal part of the lateral wall of the diencephalons.
a The pineal gland (body) or epiphysis median diverticulum of the caudal part of the
roof of the diencephalons. Proliferation of the cells in its walls solid, cone-shaped
gland.
b a phylogenetically primitive gland that often serves as a light receptor.
c Under the influence of light/dark cycles,
the pineal gland secretes (mainly at night) melatonin,
a hormone that inhibits function of the pituitary-gonadal axis
of hormonal control.

B Pituitary gland
1 The pituitary gland is ectodermal in origin.
- It develops from two sources:
a An upgrowth from the ectodermal roof of the stomodeum called the hypophysial
diverticulum
b A downgrowth from the neuroectoderm of the diencephalon called the
neurophypophysial diverticulum
2 During the 4 week of development, a hypophysial diverticulum –( Ra thke’spouc h)–projects
from the roof of the stomodeum and lies adjacent to the floor (ventral wall) of the
diencephalon.
3 By the 5 week, this pouch has elongated and has become constricted at its attachment to the
oral epithelium, giving it a nipplelike appearance. By this stage, it has come into contact with
the infundibulum (derived from the neurohypophysial diverticulum), a ventral downgrowth of
the diencephalon.
4 Infundibulum retains a neural character.
5 Asde ve l
opme ntpr oceeds ,Ra t
hke ’spouc he l
ong atestowa rdthei nfundi bulum.
While its blind end partially enfolds the infundibulum like a double-layered cup, the stalk of
Rathke ’spouc hbegins to regress.
a The outer wall of the cup thickens and assumes a glandular appearance in the
course of its differentiation into the pars distalis (anterior lobe) of the
hypophysis.
b The inner layer of the cup, which is closely adherent to the neural lobe, becomes
the pars intermedia.
c It remains separated from the anterior lobe by a slit-like residual lumen, which
represe ntsa llthatr ema insoft h eoriginallume nofRa thke ’spouc h.
6 Late in the fetal period, specific cell types begin to produce small amounts of hormones.

42
C Development of the Thyroid Gland
1 24days, An unpaired primordium of the thyroid gland appears in the ventral midline of the
pharynx between the first and second pouches.
2 Starting during the fourth week as an endodermal thickening just caudal to the median
tongue bud , the thyroid primordium soon elongates to form a prominent downgrowth
called the thyroid diverticulum.
3 Caudal extension of the thyroid diverticulum continues during pharyngeal development.
4 During its caudal migration the tip of the thyroid diverticulum expands and bifurcates form
the thyroid gland itself, which consists of two main lobes connected by an isthmus.
5 For some time the gland remains connected to its original site of origin by a narrow
thyroglossal duct.
6 By about the seventh week, when the thyroid has reached its final location at the level of
the second and third tracheal cartilages, the thyroglossal duct has largely regressed.
7 Nevertheless, in almost half the population the distal portion of the thyroglossal duct
persists as the pyramidal lobe of the thyroid.
8 The original site of the thyroid primordium persists as the foramen cecum, a small blind pit
at the base of the tongue.

D parathyroid tissue
1 By the fifth week of gestation, cells identifiable as parathyroid tissue can be recognized in
the endoderm of the solid dorsal mass.
2 The ventral elongation of the third pouch differentiates into the epithelial portion of
the thymus gland.
a The primordia of both the thymus and the parathyroid glands lose their connection with
the third pharyngeal pouch and migrate caudally from their site of origin.
b Although the parathyroid III primordia initially comigrate with the thymic primordia,
they ultimately continue to migrate toward the midline.
c There they join with the thyroid gland, passing the parathyroid primordia of the fourth
pouch to form the inferior parathyroid glands.
3 The fourth pharyngeal pouch is organized somewhat like the third, with a solid,
bulbous, dorsal parathyroid IV primordium.
a It also contains a small ventral epithelial outpocketing, which contributes a minor
component to the thymus in some species. (In humans the thymic component of the
fourth pouch is vestigial.)
b At the ventral-most part of each fourth pouch is another structure called the
postbranchial (ultimobranchial) body.
c Uncertainty surrounds the cellular origins and composition of the postbranchial bodies.
Although according to one view the postbranchial bodies arise purely from pharyngeal
endoderm, recent data suggest that neural crest cells migrate into the postbranchial
bodies and ultimately become the secretory component of these structures. (C cells in
43
 thyroid gland.)
d As with their counterparts from the third pouch, the parathyroid IV primordia lose
their connection with the fourth pouch and migrate toward the thyroid gland as the
superior parathyroid glands.
e The postbranchial bodies also migrate toward the thyroid, where they become
incorporated as parafollicular of C cells
4 Digeorge Syndrome: Congenital Thymic Aplasia ;Absence of the parathyroid glands

E Development of the suprarenal Glands

1 The cortex and medulla of the suprarenal (adrenal) glands have different origins.
a The cortex develops from mesoderm
b The medulla differentiates from neural crest cells  secretory cells of the suprarenal
medulla.
2 The cortex first becomes evident during the sixth week of development by an
aggregation of mesenchymal cells on each side, between the root of the dorsal
mesentery and the developing gonad.
a Mesenchymal cells from the mesothelium enclose the fetal cortex and give rise to the
permanent cortex. Differentiation of the characteristic suprarenal cortical zones begins
during the late fetal period.
i The zona glomerulosa and zona fasciculata are present at birth,
ii The zona reticularis is not recognizable until the end of the third year.
3 The suprarenal glands of the human fetus are 10 to 20 times larger than the adult glands
relative to body weight and are large compared with the kidneys.
a These large glands result from the extensive size of the fetal cortex.
b The suprarenal medulla remains relatively small until after birth.
c The suprarenal glands rapidly become smaller as the fetal cortex regresses
during the first year.

44
 Development of the Eye 柯翠玲 編

A Four sources:
1 Neuroectoderm of forebrain  Retina, Posterior layers of the iris,
Optic nerve
2 Surface ectoderm of the headLens of the eye, Corneal epithelium
3 Mesoderm between the neuroectoderm and the surface ectoderm Choroid sclera and
Corneal endothelium
4 Neural crest cells

B The development of the eye (Brief describes)

1 Eye development is first evident at the beginning of the fourth week of development.
2 At the cranial end of the embryo  Neural fold Optic groove (sulci)
3 Neural folds fuse to form the forebrain;
a Optic grooves evaginate to form hollow diverticulaoptic vesicles,
b Optic vesicle project from the wall of the forebrain into the adjacent mesenchyme
4 The cavities of the optic vesicles  optic stalks The cavity of the forebrain.
5 The optic vesicles  contact with the surface ectoderm.
6 Surface ectoderm  thickens  len placodes (primordia of the lenses)
7 The lens placodes sink deep to the surface ectoderm lens pits.
8 Edges of the lens pits approach each other  fuse  lose their connection with the surface
ectoderm.  spherical lens vesicles
9 The opening of each optic cup opening is large  rim is infolded around the lens.
entered the cavities of the optic cups.
10 Linear grooves- retinal (optic) fissures –ventral surface of the optic cups and along the
optic stalks.
11 The retinal fissures contain vascular mesenchyme  hyaloid blood vessels
12 The hyaloid artery:
a A branch of the ophthalmic artery, supplies the inner layer of the optic cup, the lens
vesicle. And the mesenchyme in the optic cup. The hyaloid vein returns blood from
these structures.
b As the edges of the retinal fissure fuse, the hyaloid vessels are enclosed within the
primordial optic nerve.
c Distal parts of the hyaloid vessels eventually degenerate, but proximal parts persist as
the central artery and vein of the retina.

C Development of the Retina

The retina develops from the walls of the optic cup.
1) outer, thinner layer of the optic cup retinal pigment epithelium, (Embryonic
early fetal
periods, two layers are separated by an intraretinal space)
45
 2) inner, thicker layer of the optic cup  neural retina  Photoreceptors
3) Intraretinal space  disappears  fuse, but never firm (hence, when an adult eyeball is
dissected, the neural retina is often separated from the retinal pigment epithelium.)

D Development of the ciliary body

1) The ciliary body is the wedge-shaped extension of the choroid.
2) Its medial surface projects toward the lens, forming ciliary processes.
3) The pigmented part of the ciliary epithelium  retinal pigment epithelium.
4) The nonpigmented part of the ciliary epithelium neural retina (No neural elements
differentiate)
5) The smooth ciliary muscle (focusing the lens) and the connective tissue in the ciliary body 
mesenchyme located at the edge of the optic cup in the region (between
the anterior sclera condensation and the ciliary pigment epithelium)

E Development of the Iris

1) Iris  Rim of the optic cup, which grows inward and partially covers the lens.
2) The two layers of the optic cup remain thin in this area.
3) The epithelium of the iris  both layers of the optic cup (retinal pigment
epithelium and neural retina)
4) The connective tissue framework of the iris  neural crest cells
5) The dilator pupillae and sphincter pupillae muscles of the iris  neuroectoderm of the optic
cup.  anterior epithelial cells of the iris. These smooth muscles

F Color of the Iris

1) The iris is typically light blue or gray in most newborn infants.
2) It acquires its definitive color as pigmentation occurs during the first 6 to 10 months.
3) It is the concentration and distribution of pigment-containing cells, called chromatophores, in
the loose vascular connective tissue of the iris that determines eye color.
4) If the melanin pigment is confined to the pigmented epithelium on the posterior surface of the
iris the eye appears blue. If melanin is also distributed throughout the connective tissue of
the iris, the eye appears brown.
G Development of the Lens
1) L-Maf (lens-specific Maf)  surface ectoderm.  lens placode and vescle.
2) Anterior wall of the lens vesicle cuboidal epithelium lens epithelium.
3) Posterior wall tall columnar cells
4) These cells lengthen considerably to form highly transparent epithelial cells, the Primary lens
fibers.
5) As these fibers growobliterate the cavity of the lens vesicle.
6) The rim of the lens equatorial zone  between the anterior and posterior poles of the lens.
7) The cells in the equatorial zone are cuboidal; as they elongate  lose nuclei and secondary
46
 lens fibers  added to the external sides of the primary lens fibers.
8) Secondary lens fibers continue to form during adulthood and the lens increases in diameter
9) Primary lens fibers must last a lifetime.
10) The developing lens is supplied by the distal part of the hyaloid artyer;
11) The developing lens  supplied by the distal part of the hyaloid artery
12) in the fetal period  the artery degenerates avascular the lens depends on
diffusion from the aqueous humor in the anterior chamber of the eye, which bathes its
anterior
13) The developing lens is invested by a vascular mesenchymal layer, the tunica
vasculosa lentis.
14) The anterior part of this capsule is the pupillary membrane.
15) The part of the hyaloid artery that supplies the tunic vasculosa lentis
 disappears during the late fetal period.  The tunica vasculosa lentis and
pupillary membrane degenerate; however  the lens capsule
 produced by the anterior lens epithelium and the lens fibers persists.
 lamella structure.
16) The former site of the hyaloid artery  hyaloid canal in the vitrous body (usually
inconspicuous)

H Vitreous body
1) Forms within the cavity of the optic cup.
2) It is composed of vitreous humor, an avascular mass of transparent, gel-like, intercellular
substance.
3) The primary vitreous humor is derived from mesenchymal cells of neural crest origin.
4) The primary vitreous humor does not increase, but it is surrounded by a gelatinous
secondary vitreous humor, the origin of which is uncertain
I Persistence of the hyaloid artery
1) Distal part of the hyaloid artery normally degenerates
2) Proximal part  Central artery of the retina.
3) part of the artery persists distally freely moving, nonfunctional vessel or as a wormlike
structure projecting from the optic disc
4) The hyaloid artery remnant may appear as a fine strand traversing the vitreous body.
5) In other cases, the remnant may form a cyst.
J Development of the Aqueous Chambers
1) Anterior chamber of the eye a cleftlike space that forms in the mesenchyme located
between the developing lens and cornea.
2) The mesenchyme superficial to this space forms the substantia propria of the cornea and the
mesothelium of the anterior chamber.
3) After the lens is established, it induce the surface ectoderm to develop into the epithelium of
the cornea and the conjunctiva.
47
 4) The posterior chamber of the eye develops from a space that forms in the mesenchyme
posterior to the developing iris and anterior to the developing lens.
5) When the pupillary membrane disappears and the pupil forms, the anterior and posterior
chambers of the eye are able to communicate with each other through a circumferential
scleral venous sinus. This sinus encircles the anterior chamber and is the outflow site of
aqueous humor from the anterior chamber of the eye to the venous system

K Development of the Cornea

The cornea is formed from three sources:
1) The external corneal epithelium is derived from surface ectoderm.
2) The embryonic connective tissue or mesenchyme is derived from mesoderm
3) Neural crest cells migrate from the lip of the optic cup through the embryonic connective
tissue and are transformed into the corneal endothelium.
4) Formation of the cornea induced by the lens vesicle, which acts on the surface ectoderm.

L Development of the Choroid and Sclera

1) Mesenchyme surrounding the optic cup (largely of neural crest origin)
 the choroid and the sclera.
2) The sclera develops from a condensation of the mesenchyme external to the choroid and is
continuous with the stroma (connective tissue framework) of the cornea.
3) Toward the rim of the optic cup the choroid becomes modified  the ciliary processes
4) The first choroidal blood vessels appear during the 15th week of development; by the 22nd
week, arteries and veins can be distinguished

M Development of the Eyelids

1) The eyelids develop during the sixth week of development from mesenchyme derived from
the neural crest and from two folds of skin that grow over the cornea.
2) The eyelids adhere to one another by the beginning of the 10th week , and remain adherent
until the 26th to 28th weeks.
3) While the eyelids are adherent, there is a closed conjunctival sac anterior to the cornea; when
the eyelids begin to open, the bulbar conjunctiva is reflected over the anterior part of the
sclera and the surface epithelium of the cornea.
4) The palpebral conjunctiva lines the inner surface of the eyelids.

N Development of the Lacrimal Glands

1) The Lacrimal glands develop at the superolateral angles of the orbits  a number of solid
buds from the surface ectodrm.
2) The lacrimal glands are small at birth and do not function fully until about 6 weeks; hence,
the newborn infant does not produce tears when it cries. Tears are often not present with
crying until 1 to 3 months of age.
48
O Summary of development of the eye
1) The first indication of the eye is the optic groove, which forms at the beginning of the fourth
week of development.
2) The groove deepens to form an optic vesicle that projects from the forebrain,
3) The optic vesicle contacts the surface ectoderm and induces development of the lens placode,
the primordium of the lens.
4) As the lens placode invaginates to form a lens pit and lens vesicle, the optic vesicle
invaginates to form an optic cup.
5) The retina forms from the two layers of the optic cup.
a The retina, optic nerve fibers, muscles of the iris, and epithelium of the iris and ciliary
body are derived from the neuroectoderm of the forebrain. The sphincter and dilator
muscles of the iris develop from the ectoderm at the rim of the optic cup.
b The surface ectoderm gives rise to the lens and the epithelium of the lacrimal glands,
eyelids conjunctivea, and cornea.
c The mesoderm gives rise to the eye muscles, (except those of the iris), and to all
connective and vascular tissues of the cornea, iris, ciliary body, choroid, and sclera.

49
 Development of the Ear 柯翠玲 編

A Development of the Inner Ear (Brief)

1 Otic placode develops by day 22 from surface ectoderm Invaginates to form otic fovea
2 Invaginated otic fovea folds to form otocyst Differentiates into inner ear
3 Otocyst gives rise to the components of the inner ear
a Utricle
b Saccule
c Cochlea
d Semicircular canals

B Middle and Outer Ear Development (Brief)

1 At level of first pharyngeal pouch
a Invagination of surface ectoderm
b Evagination of endoderm
2 Auditory ossicles develop by 6 week

C Development of the Internal Ear (memberane labyrinth)

1 First of the three parts of the ear to begin to develop.
2 4th week , notochord & paraxial mesoderm  stimulate  thickening of surface ectoderm-
the otic placode - appears on each side of the myelencephalon
3 Each otic placode soon invaginates and sinks deep to the surface ectoderm into the
underlying mesenchyme.  otic pit.
4 The edges of the otic pit soon come together and fuse  otic vesicle  the primordium of
the membranous labyrinth.
5 The otic vesicle soon loses its connection with the surface ectoderm, and a diverticulum
grows from the otic vesicle and elongates to form the endolymphatic duct and sac.
Two regions of the otic vesicle are now recognizable:
a) A dorsal utricular part from which the endolymphatic duct, utricle, and
semicircular ducts arise
b) A ventral saccular part, which gives rise to the saccule and cochlear duct in which the
spiral organ (of Corti) is located.
6 Three disklike diverticula grow out from the utricular part of the primordial
membranous labyrinth. The central parts of these diverticula fuse and disappear. The
peripheral unfused parts of the diverticula  semicircular ducts, which are attached to the
utricle  later enclosed in the semicircular canals of the bony labyrinth.
7 Localized dilatations, the ampullae, develop at one end of each semicircular duct.
8 Specialized receptor areas, called cristae ampullares, differentiate in these ampullae and in
the utricle and saccule (maculae utriculi and sacculi).
9 From the ventral saccular part of the otic vesicle, a tubular diverticulum -the cochlear duct
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 - grows and coils to form the membranous.
10 A connection of the cochlea with the saccule, the ductus reuniens, soon forms.
11 The spiral organ (of Corti) differentiates from cells in the wall of the cochlear duct
12 Ganglion cells of CN VIII migrate along the coils of the membranous cochlea and form the
spiral ganglion (cochlear ganglion).
13 Nerve processes terminate on hair cells.
14 The cells in the spiral ganglion retain their embryonic bipolar condition.

D Development of the Inner Ear (bony labyrinth)

1 Inductive influences from the otic vesicle stimulate the mesenchyme around the otic vesicle
to differentiate into a cartilaginous otic capsule.
2 Transforming growth factor-beta1) (TGF-beta1) may  modulating epithelial-mesenchymal
interaction in the internal ear and in directing the formation of the otic capsule.
3 As the membranous labyrinth enlarges vacuoles appear in the cartilaginous otic capsule
coalescing  perilymphatic space.
4 The membranous labyrinth is now suspended in perilymph (fluid in the peri lymphatic
space).
5 The perilymphatic space related to the cochlear duct develops two divisions, the scala
tympani and scala vestibuli.
6 The cartilaginous otic capsule later ossifies to  bony labyrinth of the internal ear.
7 The internal ear reaches its adult size and shape by the middle of the fetal period  (20 to
22 weeks).

E Development of the Middle Ear

1 Development of the tubotympanic recess from the first pharyngeal pouch.
2 The proximal part of the tubotympanic recess  pharyngotympanic tube (auditory tube).
3 The distal part of the tubotympanic recess  tympanic cavity which gradually envelops the
auditory ossicles (malleus, incus, and stapes), their tendons and ligaments, and the chorda
tympani nerve.
4 All these structures receive a more or less complete epithelial investment. An epithelial-type
organizer, located at the tip of the tubotympanic recess, probably plays a role in the early
development of the middle ear cavity by inducing programmed cell death - apoptosis.
5 During the late fetal period, expansion of the tympanic cavity gives rise to the mastoid
antrum, located in the temporal bone.
6 The mastoid antrum is almost adult size at birth; however, no mastoid cells are present in
newborn infants.
7 By 2 years of age mastoid cells  well developed  conical projections of the temporal
bones  mastoid processes.
8 The middle ear continues to grow through puberty

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 9 Development of the auditory ossicles :
1st arch cartilage Malleus + Incus;
2nd arch cartilage Stapes
10 The tensor tympani, the muscle attached to the malleus, is derived from
mesenchyme in the first pharyngeal arch and is innervated by CN V
(the nerve of this arch).
11 The stapedius muscle is derived from the second pharyngeal arch and
is supplied by CN VII (the nerve of that arch)

F Development of the External Ear

1 The external acoustic meatus develops from the dorsal part of the first pharyngeal groove.
2 The ectoderm cells at the bottom of this tube proliferate to form a solid epithelial plate 
the meatal plug.
3 Late in the fetal period, the central cells of this plug degenerate, forming a cavity that
becomes the internal part of the external acoustic meatus.
4 The external acoustic meatus attains its adult length around the ninth year.
5 The primordium of the tympanic membrane is the first pharyngeal membrane, which
separates the first pharyngeal groove from the first pharyngeal pouch .
6 The external covering of the tympanic membrane  surface ectoderm
7 The internal lining  the endoderm of the tubotympanic recess.
8 The auricle develops from six mesenchymal proliferations in the first and second
pharyngeal arches.
9 Prominences, called auricular hillocks, surround the first pharyngeal groove
10 As the auricle grows, the contribution by the first arch is reduced.
11 The lobule (earlobe) is the last part to develop.
12 The auricles begin to develop at the base of the neck
13 As the mandible develops, the auricles move to their normal position at the side of the head

G Summary of development of the ear

1 The otic placodes and the otic vesicle develop from the surface ectoderm during the fourth
week.
2 The vesicle develops into the membranous labyrinth of the internal ear.
The otic vesicle divides into two parts:
a A dorsal utricular part, which gives rise to the utricle, semicircular ducts
b A ventral saccular part, which gives rise to the saccule and cochlear duct
3 The cochlear duct gives rise to the spiral organ.
4 The bony labyrinth develops from the mesenchyme adjacent to the membranous
labyrinth.
5 The epithelium lining the tympanic cavity, mastoid antrum, and pharyngotympanic tube is
derived from the endoderm of the tubotympanic recess, which develops from the first
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 pharyngeal pouch.
6 The auditory ossicles (malleus, incus, and stapes) develop from the dorsal ends of the
cartilages in the first two pharyngeal arches.
7 The epithelium of the external acoustic meatus develops from the ectoderm of the first
pharyngeal groove.
8 The tympanic membrane is derived from three sources:
a endoderm of the first pharyngeal pouch
b Ectoderm of the first pharyngeal groove
c Mesoderm between the layers listed above
9 The auricle  six auricular hillocks  mesenchymal prominences around the margins of
the first pharyngeal groove  These hillocks fuse to form the auricle.

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