QUIZ 1

Introduction

-Epiblast --> Primordial yolk sac via primitive streak --> Genital ridge via allantois

Testes
Week 7: Gonadal/sex cords --> solid testis/seminiferous cords due to TDF/SRY
Puberty: Primordial germ cells --> spermatogonia
Solid testis/seminiferous cords --> Seminiferous tubules
-Antimullerian hormone (Sertoli cells) stops paramesonephric duct from forming

Ovaries
Week 7: Cortical/sex cords --> Ovaries in the absence of TDF
Primordial germ cells --> Oogonia (in 1° follice)

Mitosis
-Division into 2 daughter cells that are genetically identical to the parent cell and that
maintain the same chromosome number (i.e. 2N-->4N-->2N)
-PGC (46, 2N) --> Oogonia OR Type B spermatogonia (46, 2N)

Meiosis
-Oogonia/Type B spermatogonia (46, 2N) --> 1° oocyte/spermatocyte (46, 4N) --> 2°
oocyte/spermatocyte (23, 2N) --> Ovum/spermatid (23, 1N)

-In oogenesis (females), meiosis I generates a 2° oocyte and polar body (23, 2N), which go
on to form a mature ovum and 3 polar bodies (23, 1N)
-In month 3, some oogonia enter meiosis and are arrested at prophase I as 1° oocytes
-1° oocytes do not finish meiosis I until puberty
-Primordial follicle w/ immature 1° oocyte --> Primary follicle w/ 1° oocyte -->
Secondary follicle with 1° oocyte --> Tertiary follicle w/ 2° oocyte --> Ovulated 2°
oocyte (23, 2N)
-Proliferative phase:
-Rising level of estrogen causes endometrium to thicken
-Ovulation on day 14 due to LH surge = meiosis I is completed and meiosis
II is initiated
-After ovulation, granular cells + theca interna cells + LH --> corpus luteum
-Secrete progesterone + estrogen to help uterine endometrium grow
-Secretory phase:
-Inhibition of uterine contraction
-If NO fertilization: rising level of progesterone inhibits GnRH which, in turn,
inhibits further progesterone production (negative feedback)
-Menstrual phase:
-NO fertilization: corpus luteum --> corpus albicans
-Decreased levels of progesterone + uterine contraction = menstrual bleeding
-Fertilization: corpus luteum --> corpus luteum of pregnancy due to hCG
-After 20 weeks of pregnancy, placenta takes over production of progesterone +
estrogen
-Large doses of estrogen for several days after unprotected sex prevent implantation

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 -Pregnancy: EPF detected in mother’s serum by week 2 and hCG in urine by week 3

VS.
-In spermatogenesis (males) on the other hand, meiosis I produces two 2° spermatocytes (23,
2N) which in turn generate 4 spermatids (23, 1N)
-Spermatozoa/Sperm form from via spermiogenesis process

Assisted Reproductive Techniques

-IVF: ova are removed from a woman’s ovary and fertilized with sperm in a lab, then
returned to the woman’s uterus
-GIFT: oocyte and sperm introduced into the ampulla of the uterine tube
-ZIFT: fertilized oocytes are placed in the ampulla of the uterine tube
-ICSI: manipulation technique used to inject a single sperm into each egg – adopted to
overcome oligozoospermia

Week 1
-Day 1: Fertilization:
1) Penetration of corona radiata (free diffusion by capacitated sperm)
2) Penetration of zona pellucida via acrosomal reaction
-Release of acrosin and trypsin-like substances from sperm’s acrosomal
region to digest zona pellucida and plasma membrane of the ovum
3) Fusion of oocyte + sperm cell membranes
-Sperm nucleus, mitochondria and flagellum cross the membrane but
mitochondria and tail degenerate
-Zona reaction + cortical reaction of oocyte prevent fusion with
other sperms
-Entry of sperm allows oocyte to complete meiosis II to form mature ovum
and second polar body
-Male and female pronuclei (23, 1N) fuse to form zygote (46, 2N)
-Day 2/3: Blastula forms via mitotic division of zygote and cells divide to form morula
-2 cells --> 4 --> 8 --> 16 (morula) --> 32
-Zona pellucida remains, preventing “overgrowth” of morula
-Day 4: Blastocyst
-Inner cell mass --> embryoblast (embryo)
-Outer cell mass --> trophoblast (fetal side of placenta, see next page)
-Day 5:
-Zona pellucida degenerates resulting in rapid increase in size of blastocyst
-Blastocystic cavity --> Primitive/primary yolk sac
-Day 6: Implantation begins
-Uterine endometrium undergoes decidual reaction
-Normal implantation site: posterior superior wall of uterine body
-Trophoblast --> inner cytotrophoblast (CTB)
--> outer syncytiotrophoblast (STB) --> secrete hCG on day 8
-Day 7: Implantation continues
-Blastocyst burrows within endometrium

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Week 2
-Day 8:
-Decidual cells of the endometrium store glycogen and lipids which nourish the
embryo
-Decidua basalis --> maternal part of placenta

-Embryoblast --> epiblast (ECTODERM)--> primitive amniotic cavity

--> hypoblast (ENDODERM)--> primitive/primary yolk sac cavity

-Trophoblast --> cytotrophoblast

--> syncytiotrophoblast
-Day 9/10:
-Small vacuoles emerge which come together to form lacunae
-Endometrial blood vessels fill these lacunae with oxygenated blood and
uterine glandular secretions (embryotroph) for additional embryoblast
nutrition via diffusion
-Deoxygenated blood with embryoblast waste is removed via veins
= uteroplacental circulation
-Fibrin coagulum plug closes entry site of embryoblast/trophoblast into endometrium
-Day 11/12:
-Hypoblast --> Extraembryonic mesoderm --> parietal (somatopleuric)
-covers CTB, connecting stalk
+ outer amniotic cavity
--> visceral (splanchnopleuric)
-lines yolk sac
--> Secondary yolk sac (NO nutritional effect)
-Extraembryonic coelom --> chorionic cavity
-Parietal extraembryonic mesoderm+STB+CTB --> chorion (fetal side of placenta)
-Primary yolk sac --> Exocoelomic cyst
-Epiplast + Hypoblast fuse to form prechordal plate (future forebrain, thus
establishing rostral-caudal orientation)
-Day 13/14:
-Parietal extraembryonic mesoderm --> primary chorionic villi (extensions of CTB)
-Connecting stalk becomes umbilical cord

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Week 3
-Appearance of primitive streak from migration of epiblast cells is first sign of gastrulation
-Primitive streak elongates to form the notochord (primitive node=cranial end, pit and
groove=caudal end)
-Prenotochordal cells (mesoderm) --> prechordal plate --> notochordal process -->
notochordal canal (w/ lumen) --> notochordal plate (w/ hypoblast cells) --> notochord
-Notochord induces neuroectoderm --> neural plate --> neural groove --> neural fold
--> neural tube (separates from surface ectoderm) --> spinal cord
-Notochord becomes the nucleus pulposes of IVD and aplical ligament of
dens C2 and is involved in the development of the axial skeleton
-Communication between neural tube and amniotic cavity via neuropores
-Neuroectoderm cells lying along edges of neural folds form neural crest cells
(DRG, meninges, melanocytes of skin, suprarenal medulla, parafollicular cells of
thyroid gland)
-Differentiation of epiblast into three germ layers (gastrulation)
Epiblast cells --> intraembryonic endoderm --> mesoderm --> ectoderm/
neuroectoderm
-Intraembryonic mesoderm does NOT cover prechordal plate (future nervous
system), buccopharyngeal membrane (future oral cavity), cloacal membrane
(future anus) or notochord (nervous system development)
-Polarity is established
-Continuous migration of cells from the primitive streak toward cephalic end,
causing embryonic disc to appear broader cephalically and more narrow at its
caudal end
-Cephalic gastrulation ends (differentiation only) while caudal germ layer
formation continues --> embryo develops cephalocaudally
-By the end of week 4, the primitive streak regresses

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Trilaminar Disk

EMBRYONIC PERIOD: WEEK 3-8

-Notochord induces paraxial mesoderm (somites + somitomeres)
-Sclerotome --> axial skeleton + neurocranium
-Dermomyotome --> dermatome --> dermis of skin
--> myotome --> muscles
-Intermediate mesoderm --> urogenital structures
--> nephrogenic duct of developing kidney
--> suprarenal cortex
-Lateral plate mesoderm (INTRAembryonic) --> thoracic and abdominal cavities (pleura,
pericardium, peritoneum)
-Head fold --> cephalic end (ventral) --> foregut (part of yolk sac)
-Tail fold --> caudal end (dorsal) --> hindgut (part of yolk sac + allantois)
-Lateral folds --> R and L ends --> vitelline duct (degenerates in month 2/3)

-Primary chorionic villi = 2 layers = STB + CTB

-Secondary chorionic villi = 3 layers = STB + CTB + inner layer of extraembryonic
mesoderm
-Tertiary chorionic villi = 3 layers = STB + CTB + inner layer of extraembryonic mesoderm
w/ capillaries

-Placental membrane/barrier separated the maternal and fetal blood at villi and consists of 4
layers:
1) STB
2) CTB
3) Extraembryonic mesoderm of villi
4) Endothelium of fetal capillaries
-Placenta is a feto-maternal organ site where nutrients and gas exchange between mother and
fetus occur
-Fetal part developed from chorion
-Umbilical cord is attached to the fetal surface
-NO cotyledons
-Maternal part derived from desidua basalis of uterine endometrium
-Cotyledons are where feto-maternal gas exchange occurs

FETAL PERIOD: WEEK 9-40

-Parturition:
-Effacement: myometrium thickens in upper portion of uterus and becomes thinner
and shorter in the lower region, cervix dilates via uterine contractions
-Delivery of fetus as well as placenta and fetal membranes 30 minutes after birth via
uterine contractions and increases in intra-abdominal pressure
-Growth and maturation of tissues + addition of fat

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Clinical Correlations

-Hydatidiform mole: abnormal growth in uterus containing a nonviable or non-developing

embryo but trophoblast continues to develop, producing excessive amounts of hCG
-Complete: NO female pronucleus + duplication of male DNA
-Partial: Female pronucleus present + 2 sperms (dispermy)/duplication of male DNA

-Allantoic cysts: remnants of extraembryonic portions of allantois found between fetal

umbilical vessels

-Patent urachus/allantoic diverticulum: if lumen of allantois fails to obliterate, it remains

as patent urachus connecting the apex of the urinary bladder to the umbilicus
-Weeping umbilicus: urine may dibble from the umbilicus through the patent
urachus

-Polyhydramnios: too much amniotic fluid, usually idiopathic but can be caused by maternal
diabetes, congenital malformations such as anencephaly and esophageal atresia; associated
with GI, CNS, cardiovascular and urogenital system abnormalities

-Oligohydramnios: too little amniotic fluid, usually caused by renal agenesis or amnion
rupture during trauma and can lead to club foot and pulmonary hypoplasia

-Dizygotic (fraternal) twins: 2 ovum are ovulated and fertilized by 2 sperms

-2 chorionic sacs, 2 amnions, 2 placentas

-Monozygotic (identical) twins: 1 fertilized zygote that splits into 2

A) Separation at two-cell stage of blastula: separate chorionic sacs, amnions and
placentas
B) Separation at early blastocyte stage: common placenta and chorionic cavity but
separation amniotic sacs
C) Separation at bilaminar germ disc stage: shared placenta, chorionic sac and
amniotic cavity

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QUIZ 2

Body Cavity Development

-Coelomic spaces + head/tail/lateral foldings --> Primitive body cavity

-Primitive body cavity divides lateral plate mesoderm into visceral and parietal layers
-Lungs separate primitive body cavity into pulmonary-abdominal cavity and pericardial
cavity
-Diaphragm separates pulmonary and abdominal cavities
-Septum transversum is mesoderm between thoracic and abdominal cavities
-Pericardioperitoneal canals: openings between pulmonary and abdominal cavities
where lung/bronchial buds will grow
-As lungs expand, they become too large for these canals and begin to enter
mesenchyme of body wall
-While the pulmonary cavities are forced anteriorly, pleuropericardial folds
move posteriorly and medially
-Pleuropericardial folds contain the common cardinal veins (which
drain into SVC) and phrenic nerves
-Pleuropericardial membranes eventually fuse with mesentery of
esophagus and septum transversum (R before L)
-Myoblasts from somites at C3-C4-C5 fuse with these membranes
-Pleuropericardial membranes form fibrous and parietal pericardium
-Pleuroperitoneal membrane closes pericardioperitoneal canals

Mini Summary:
Diaphram is composed of:
-Septum transversum --> central tendon of diaphragm
-2 pleuroperitoneal membranes --> posterior part of diaphragm
-Somites C3-C4-C5 --> muscular part of diaphragm
-Mesentery of esophagus --> crura of diaphragm
-Mesenchyme of thoracic body wall --> most peripheral part of diaphragm

-Parietal LPM --> Parietal layer of pericardium, pleura and peritoneum

--> Dorsal mesentery of the foregut + Mesentery of midgut/hindgut
-Suspends gut tube from posterior abdominal wall into peritoneal cavity
-Visceral LPM --> Visceral layer of pericardium, pleura and peritoneum
--> Ventral mesentery of foregut
-Falciform, coronary and triangular ligaments are the only remaining ventral
mesentery left after development
-Attaches to anterior abdominal wall

-Head fold shifts the heart, buccopharyngeal membrane and pericardial cavity ventrally and
incorporates part of the yolk sac as foregut
-Lateral fold formation is followed by constriction of the yolk sac to form the vitelline duct
and midgut
-Vitelline duct incorporates into umbilical cord/connecting stalk

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Clinical Correlations

VENTRAL BODY WALL DEFECTS:

-Ectopia cordis: failure of lateral fold to close midline in thoracic region causing heart to lie
outside abdominal body cavity

-Gastroschisis: intestinal loops herniate into amniotic cavity due to failure of body wall to
close in abdominal region
-NOT associated with chromosome abnormalities

-Omphalocele: portions of midgut tube herniate into umbilical cord (normal) but in this case,
they fail to return to the abdominal cavity
-NOT considered a cause of defective body wall closure
-Chromosome abnormalities present
-Associated with elevated alpha-fetoprotein (AFP) concentrations

-Bladder exstrophy: abnormal body wall closure in pelvic region leading to exposure of
bladder

-Cloacal exstrophy: abnormal body wall closure in pelvic region leading to exposure of
bladder and rectum

-Cantrell PENTAlogy: failure of ventral wall to close beginning at caudal end of sternum
and extending into upper abdomen
-Associated with 5 main defects:
1) Defective closure of supraumbilical abdominal wall (omphalocele)
2) Defect in anterior portion of diaphragm and diaphragmatic pericardium
3) Sternal defects
4) Ectopia cordis
5) Cardiac malformations (e.g. ventricular septal defect or diverticulum of L
ventricle)

CONGENITAL DIAPHRAGMATIC HERNIAS (CDH):

-Bochdalek hernia: posterolateral defect of diaphragm due to failure of the

pericardioperitoneal canals to close during development, usually present on L side

-Morgagni hernia: occurs in anterior midline through sternocostal hiatus of diaphragm

*Pulmonary hypoplasia: a result of CHD, causing lungs to be compressed by

abnormally positioned abdominal viscera thus preventing normal development and
expansion at birth

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Development of the Musculoskeletal & Integument Systems + Limb Development

-Paraxial mesoderm --> Sclerotome --> Cartilage, bone + joints of axial skeleton
--> Vertebrae + Intervertebral disc
--> Ribs, sacrum + coccyx
--> Membranous + Cartilagenous neurocranium
--> Tendons
--> Dermomyotome --> Dermatome --> Back dermis + hypodermis
--> Myotome --> Muscles of axial (head) +
appendicular regions
(ventrolateral myoblasts)*
--> Intrinsic back muscles
(dorsomedial myoblasts)**

-C4-C8 + T1: forelimb muscles (arms)

-L1-L5 + S1-S2: hindlimb muscles (legs)

*Ventrolateral myoblasts --> hypomere --> Forelimb muscles + 3 layers of body wall
-Innervated by ventral primary ramus

**Dorsomedial myoblasts --> epimere --> Intrinsic back muscles

-Innervated by dorsal primary ramus

-Parietal LPM --> Cartilage, bones + CT of appendicular skeleton (forelimb before

hindlimb)
--> Sternum
--> Costal cartilage
--> Smooth muscle of blood + lymphatic vessels

-Limb mesoderm induces a thickening of the surface ectoderm at the tip of the limb bud
(a.k.a. apical ectodermal ridge, AER), which in turn induces adjacent mesoderm to
continue to proliferate and remain UNdifferentiated in the proximal-distal limb axis (a.k.a.
proximal zone)
-Mesoderm will begin to differentiate once AER has migrated past it
-Induces the formation of limb-specific ectodermal specializations = nails
-Retinoic acid from cells of zone of polarizing activity (ZPA) directs cranial-caudal
orientation of differentiation
-Brachial plexus innervates upper limbs
-Arterial supply development in upper limbs:
1) subclavian a. --> common interosseus a. --> median a. --> radial a.
--> ulnar a.
2) deep arteries of arm + joint arteries
-Lumbosacral plexus innervates lower limbs
-Arterial supply development in lower limbs:
1) common iliac a. --> external iliac a. --> femoral a. --> popliteal + deep artery of thigh
--> posterior tibial + fibular artery
--> internal iliac a. --> umbilical a. --> ischiadic artery (regresses)

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 --> anterior tibial a. + inferior gluteal a. + foot anastomosis

-Visceral LPM --> Cardiac muscle

--> Smooth muscle of GI

-Neural crest cells --> Pharyngeal arches 1 + 2 --> Membranous viscerocranium (face)
(CN V-3 + CN VII) --> Cartilagenous viscerocranium
(styloid, upper hyoid, middle ear
bones)
--> Pharyngeal arch 3 (CN IX) --> rest of hyoid
--> Pharyngeal arches 4 + 6 (CN X) --> cartilage of larynx
--> Melanocytes (pigmentation of epidermis of skin and hair)

EXCEPTION
Muscles of the head NOT formed by pharyngeal arches:
-Tongue: innervated by CN XII
-Extrinsic eye muscles: innervated by CN III, IV + VI

-Neuroectoderm --> Sphincter + dilator muscles of the pupil

--> Mammary + sweat glands

-Ectoderm --> Stratified epidermis (periderm) --> Stratum corneum

--> Stratum germinativum --> Epidermal ridges --> Palm + sole creases

Clinical Correlations

CONGENITAL DEFECTS OF VERTEBRA:

-Spina bifida: lack of induction signals of the transverse axis of spinal cord results in failure
of neural arches to develop or close

-Scoliosis: spinal column bends laterally usually due to non/poor formation of vertebral body
or due to ½ of vertebrae to form (hemivertebra)

DEFECTS OF CRANIAL VAULT:

-Cranioschisis: posterior cranial vault fails to form due to neuropore opening in back of head
allowing brain tissue to be exposed to amniotic fluid and resulting in brain degeneration
(anecephaly)

-Cranial meningocele: herniation of meninges

-Meningoencephalocele: herniation of brain tissue and meninges

DEFECTS ASSOCIATED WITH MUSCLE:

-Duchenne muscular dystrophy: lack of protein dystrophin resulting in muscle fibers that
are more susceptible to damage

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DEFECTS NOT ASSOCIATED WITH BONE DEFECTS:

-Poland anomaly: partial or total absence of pectoralis major muscle

-Prune belly syndrome: atrophy of abdominal wall musculature resulting in distended

abdomen

DEFECTS IN LIMB DEVELOPMENT:

-Micromelia: all segments of the limb are present but abnormally short

-Brachydactyly: digits are shortened

-Syndactyly: two or more fingers are fused

-Polydactyly: the presence of extra fingers or toes

-Ectrodactyly: absence of digit

-Cleft hand and foot: fusion of digits

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Development of the Gastrointestinal & Respiratory Systems

GI Tract: Foregut, Midgut + Hindgut

-Endoderm --> lumen/gut tube with cells, glands + villi
--> Endothelium of esophagus, duodenum, liver, gall bladder, cystic duct,
bile duct + pancreas
--> Mucous membrane of rectum + upper part of anal canal

-Paraxial mesoderm --> Mouth to upper esophagus + anus

-Visceral LPM --> Inner gut wall of esophagus, duodenum + pancreas

--> Outer gut wall of esophagus, duodenum + pancreas
--> Smooth muscle + blood vessels of liver, gall bladder, cystic duct +
bile duct
--> Musculature of rectum

-Parietal LPM --> Septum transversum --> CT covering (stroma) of liver

-Ectoderm (a.k.a. proctoderm) --> Mucous membrane of lower 1/3 of anal canal

Mouth + Pharynx
|
| 1) Pharyngeal Foregut (PG)
|
Respiratory diverticulum
|
| 2) Foregut Proper
|
Liver + Dorsal pancreatic buds
|
| 3) Midgut
|
Transverse colon
|
| 4) Hindgut
|
Cloacal membrane

Foregut structures: mouth, pharynx, respiratory organs, esophagus, stomach, 1st and ½ of
2nd parts of duodenum, liver, gall bladder + pancreas
-Main arterial supply from celiac trunk
-Parasympathetic innervation from CN X
-Sympathetic innervation from thoracic + lumbar spinal nerves

Esophagus:
-Tracheoesophageal septum separates primitive esophagus (dorsal) from
respiratory diverticulum (ventral)

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 -Upper 2/3 made up of striated muscle while lower 1/3 is smooth muscle

Stomach:
-Rotation causes superior (esophageal) end to move left and inferior (pyloric)
end to move right

Duodenum:
-Rotates to the right and becomes retroperitoneal (EXCEPT 1” of 1st part
remains intraperitoneal)

Liver, Gall Bladder + Bile Duct:

-Ventral diverticulum --> Hepatic diverticulum

Pancreas:
-Ventral pancreatic bud --> Head of pancreas
--> Uncinate process
--> Proximal part of pancreatic duct

-Dorsal pancreatic bud --> Rest of pancreas (body, tail, etc.)

--> Distal part of pancreatic duct

*Spleen and adrenal glands are non-endodermally derived organs that are formed mainly
from mesodermal cells. The medulla of the adrenal gland is made from neural crest cells.

Midgut structures: ½ of 2nd, 3rd and 4th parts of duodenum, jejunum, ileum, cecum,
appendix, ascending colon + proximal 2/3 of transverse colon
-Main arterial supply from superior mesenteric artery
-Parasympathetic innervation from CN X
-Sympathetic innervation from thoracic + lumbar spinal nerves
-Elongation of midgut and primary intestinal loop causes herniation into yolk sac
(normal) and formation of two limbs surrounding SMA:

Rostral limb (R) --> Distal duodenum, jejunum + most of ileum

Caudal limb (L) --> Rest of ileum, cecum, ascending colon + part of transverse colon

-Herniated loop eventually returns to abdominal cavity following 270° rotation

and regression of the kidney, reduced growth of the liver and expansion of the
abdominal cavity
-Further elongation of midgut results in coiling of small intestine

Hindgut structures: distal 1/3 of transverse colon, descending colon, sigmoid colon, rectum
+ anal canal
-Parasympathetic innervation from pelvic splanchnic nerves
-Sympathetic innervation from thoracic + lumber spinal nerves

Respiratory System

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-Laryngotracheal groove in larynx --> Laryngotracheal diverticulum --> Tracheobronchial
diverticulum --> Lung buds --> Bronchial buds (primary bronchi) --> Secondary bronchi (3
on R and 2 on L) --> Tertiary bronchi --> Respiratory bronchioles
-Cranial part of tracheobronchial diverticulum --> Larynx
-Development and maturation of lungs:
1) Pseudoglandular period (1-17 weeks)
-Terminal bronchioles have NO respiratory bronchioles and NO alveoli so
NO respiration is possible
2) Canalicular period (16-25 weeks)
-Respiratory bronchioles develop and respiration becomes possible, although
the chances of survival are poor
3) Terminal sac period (25 weeks-birth)
-Terminal and alveolar sacs form with capillaries coming in close contact
-Type I pneumocytes act in gas exchange while Type II pneumoncytes
appear later and secrete surfactant to counteract the surface tension forces,
thus facilitating expansion of terminal sacs
4) Alveolar period (birth-8 years old)
-Mature alveoli with well-developed epithelial and endothelial contacts
present
-Adequate pulmonary vasculature and sufficient surfactant levels are critical
to survival of premature infants
-At birth, developing lungs are half-filled with amniotic fluid
-Decreased pulmonary resistance and increases systemic resistance

Clinical Correlations

DEFECTS IN DEVELOPMENT OF THE FOREGUT:

-Esophageal atresia: improper esophageal recanalization or defective tracheoesophageal

septum resulting in “blind pouch”

-Esophageal stenosis: not complete closure but narrowing of esophagus

-Congenital hiatal hernia: stomach is pulled up through esophageal hiatus of the diaphragm
due to short esophagus

-Congenital hypertrophic pyloric stenosis: increase size of the circular muscles of the
pyloric sphincter resulting in projectile vomiting of food without bile

-Duodenal atresia: obliterated lumen of duodenum does NOT recanalize causing blockage
and resulting in gas filling up the stomach and duodenum thus preventing normal absorption
of amniotic fluid = projectile vomiting with bile

-Extrahepatic atresia: improper canalization of the bile duct

-Annular pancreas: two parts of the ventral bud rotate in opposite directions constricting the
2nd part of the duodenum

DEFECTS IN DEVELOPMENT OF THE MIDGUT:

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-Situs inversus: thoracic and abdominal viscera normally seen on the right side are found on
the left, and vise versa

-Malrotation of the gut

-Volvulus or SMA syndrome: ligament of Treitz is too short, obstructing the duodenum

-See Omphalocoele and Gastroschisis above

-Meckel’s diverticulum: a small portion of the vitelline duct persists, forming an

outpocketing of the ileum

-Umbilical fistula: vitelline duct fails to disappear and remains patent over its entire length,
causing direct communication between umbilicus and intestinal tract and demonstrating fecal
discharge at the umbilicus

DEFECTS IN DEVELOPMENT OF THE HINDGUT:

-Rectoanal atresia and fistula: ectopic positioning of the anal opening due to a short
posterior cloacal membrane causes hindgut to either end as a blind sac or open into the
vagina or urethra

-Imperforate anus: lower end of the GI tract fails to open into the exterior due to persistence
of the anal membrane and congenital atresia of the lower part of the rectum (rectoanal
atresia)

-Congenital megacolon (Hirschsprung’s disease): a portion of the colon remains as an

aperistaltic zone due to congenital agenesis of the nerve cells in the myenteric and
submucous plexus, obstructing the large gut and preventing stool from passing

DEFECTS IN DEVELOPMENT OF THE RESPIRATORY SYSTEM:

-See Esophageal atresia above

-Tracheoesophageal fistula: abnormal connection between the trachea and esophagus

-Respiratory distress syndrome: due to a deficiency in surfactant associated with hyaline

membrane disease in which the alveolar surfaces of the lungs are coated with a glassy hyaline
membrane

15
Development of the Cardiovascular System

-Epiblast --> Visceral LPM Cardiac progenitor cells --> Cardiac myoblast --> Myocardium
--> Blood islands --> Primitive blood
vessels + cells
--> Cardiac jelly
--> Proepicardial cells --> Epicardium/
Visceral
pericardium
--> Coronary a.

-Vasculogenesis: formation of blood vessels from blood islands

-Blood islands are also involved in uteroplacental circulation via extraembryonic
visceral mesoderm surrounding yolk sac, connecting stalk and chorion
-Angiogenesis: formation of blood vessels from pre-existing vessels

-Mesoderm --> Hemangioblast aggregates --> Angioblasts (endothelial precursor cells) +

Hematopoietic stem cells (blood cells) in
blood islands

-Bilateral pericardial coelom --> Pericardial cavity

-As the heart bulges into pericardial cavity, its attachment to the dorsal mesocardium
rips away forming transverse pericardial sinus

-Lateral folds fuse heart tubes together EXCEPT at its caudal position (sinus venosus)
-This end is suspended by septum transversum
-Cranial end of heart tube is called truncus arteriosus and is suspended by undifferentiated
parietal LPM

-Fused single heart tube has a series of dilatations:

-Bulbus cordis (primitive ventricles) --> Truncus arteriosus --> Aorta + Pulmonary trunk
--> Conus cordis (outflow track for both ventricles)

*Bulbus cordis and primitive ventricles grow faster than others and truncus arteriosis and
sinus venosus are anchored by aortic sac and venous attachments causing the tube to fold on
itself forming a U --> S shaped cardiac loop

-Atrioventricular canal + Bulbus cordis --> Common canal of the undivided heart (NO septa)

-Mesenchymal cells + Dorsal/Ventral endocardial cushions = Septum intermedium

-Septum intermedium divides atrioventricular canal into L and R AV canals
-Septum primum grows down toward septum intermedium dividing the atria
-Foramen primum + foramen secundum allow continuous flow of oxygenated
blood between atria

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 -Septum secundum grows down almost covering foramen secundum and forming
foramen ovale
-After birth, increased pressure in the L atrium fuses valve of foramen ovale to upper
limb of septum secundum closing the foramen to form fossa ovale

-Neural crest cells --> Conotruncal ridge --> Conotruncal septum + Membranous part of IV
septum = separates bulbus cordis and truncus arteriosis to form aorta and pulmonary trunk
by rotating at 180° angle

-R anterior cardinal vein --> part of SVC

--> R brachiocephalic vein
--> R internal jugular
*Drain head and neck
-L anterior cardinal vein --> L brachiocephalic vein
--> L internal jugular

----------------------------------------------------------------------------------------------------------------

-R posterior cardinal vein --> R supracardinal vein --> Azygous vein

*Drain trunk
-L posterior cardinal vein --> L supracardinal vein --> Hemiazygous vein

----------------------------------------------------------------------------------------------------------------

-L + R subcardinal vein anastomosis --> L renal vein + renal segment of IVC

-L subcardinal vein --> L gonadal vein

----------------------------------------------------------------------------------------------------------------

-L + R sacrocardinal vein anastomosis --> L common iliac

-R sacrocardinal vein --> rest of IVC

----------------------------------------------------------------------------------------------------------------

-R vitelline vein --> Portal vein + SMV + R hepatic vein + hepatic segment of IVC
*Drain yolk sac
-L vitelline vein --> Splenic vein + IMV + L hepatic vein + parts of sinusoids

----------------------------------------------------------------------------------------------------------------

-R umbilical vein degenerates in week 7

*Drains placenta
-L umbilical vein --> Ductus venosus --> Ligamentum teres hepatis + Ligamentum venosum

Right Atrium
-Sinus venarum: smooth part formed by R horn
-Pectinate muscles: rough part formed from remaining R primitive atrium

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 -Crista terminalis (internal) + terminal sulcus (external) separate these two areas
-R sinuatrial valve --> Crista terminalis (posteriorly)
--> Valves of IVC + Coronary sinus (inferiorly)
-L sinuatrial valve + Septum secundum = intra-atrial septum
-R sinuatrial valve + L sinuatrial valve = Septum spurium (regresses)
Left Atrium
-Dorsal L atrial wall --> Primordial pulmonary veins = smooth part
-Trabeculated auricle: formed from remaining L primitive atrium

Ventricles

-Enlargement of the ventricular walls with primordial interventricular septum form the adult
muscular part of the interventricular septum
-Septum intermedium and interventricular septum are connected by an interventricular
foramen until week 7
-Muscular part of IV septum + bulbuventricular flange (merged together by
endocardial cushions) = Membranous part of IV septum
-Interventricular foramen is closed off by the membranous part of IV septum

-Proliferation of dense mesenchyme from cardiac jelly --> AV valves (bicuspid + tricuspid)
-Right, left + lateral endocardial cushions --> aortic + pulmonary semilunar valves (truncus
swellings)
-Primitive atrium acts as the interim pacemaker of the heart until the SA node takes over in
week 5

-Venous blood flow:

Umbilical vein --> Pulmonary vein ---------|
Vitelline vein --> Hepatic + Portal veins ---|-------> Sinus venosus --> Common atria
Common cardinal vein --> SVC + IVC -----|

-Arterial blood flow:

Common ventricles --> Truncus arteriosus --> Aortic sac (aortic arch + great vessels)
--> Dorsal sac (descending aorta)

-Pharyngeal arch 1 --> Maxillary artery then disappears

--> External carotid artery
-Pharyngeal arch 2 --> Stapedial arteries then disappears
-Pharyngeal arch 3 --> R + L common carotid artery
--> Internal carotid artery
-Pharyngeal arch 4 --> Arch of aorta (between L common carotid and L subclavian artery)
--> R subclavian artery + C7 intersegmental artery
-Pharyngeal arch 5 --> disappears
-Pharyngeal arch 6 --> R + L pulmonary artery
--> Ductus arteriosus --> Ligamentum arteriosum

-Lymphatic System:
-2 jugular lymph sacs --> Head, neck and upper limbs
-2 iliac lymph sacs --> Lower trunk + limbs
-1 retroperitoneal lymph sac

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 -1 chyle cistern lymph sac

-Inferior part of R thoracic duct + Superior part of L thoracic duct = Thoracic duct
-Superior part of R thoracic duct --> R lymphatic duct

Other lymphatic organs:

-Palatine tonsil
-Tubal tonsil
-Pharyngeal tonsil
-Lingual tonsil

Clinical Correlations

DEFECTS IN ORIENTATIONAL DEVELOPMENT OF HEART:

-Dextrocardia: congenital defect where heart apex is located on right side of body due to
improper rotation of the heart tube

-Dextrocardia of embryonic arrest: heart is slightly shifted more to the right than normal

-Dextrocardia situs inversus: heart is a mirror image of normal heart and on the right side

-Dextrocardia situs inversus totalis: all viscera are reversed, resulting in congenital heart
defects

-See Cantrell’s Pentalogy above

ATRIAL SEPTAL DEFECTS:

-Ostium secundum atrial septal defect (ASD): excessive reabsorption of septum primum or
incomplete development of septum secundum causing mixing of oxygenated and
deoxygenated blood

-Ostium primum ASD: non-fusion of septum primum with septum intermedium

-Patent foramen ovale (PFO): foramen ovale doesn’t seal at limbus causing mixing of
oxygenated and deoxygenated blood

-Hypoplastic L heart syndrome: premature closure of foramen ovale prevents blood from
reaching L heart resulting in its underdevelopment and enlargement of the R heart

DEFECTS IN INTERVENTRICULAR SEPTUM DEVELOPMENT:

-Membranous IV septal defect: muscular and membranous septal portions fail to fuse

-Muscular IV septal defect

19
DEFECTS IN SEPTATION OF OUTFLOW VESSELS:

-Persistent truncus arteriosis: occurs when conotruncal ridges fail to form, combining the
aorta and pulmonary regions

-Abnormal location of conotruncal septa: conotruncal septum grows straight down instead
of at a 180° twist
-Double outlet right ventricle: abnormal truncal separation so that both aorta and
pulmonary trunk arise from right ventricle causing deoxygenated blood to be sent to body

-TETRAlogy of Fallot: caused by chromosome 22 deletions and diGeorge syndrome

1) Pulmonary stenosis (narrow R ventricle)
2) IV septal defect
3) Overriding of the aorta
4) R ventricular hypertrophy

-Patent ductus arteriosus: ductus arteriosus does not close due to large differences in
pulmonary and aortic pressure, causing it to stay open and thus allowing continued blood
flow through it

-Coarctation of aorta: aortic lumen distal to L subclavian artery is significantly narrowed

20
QUIZ 3

Development of Urogenital System

URINARY SYSTEM:
-Intermediate mesoderm --> CT, smooth muscle, epithelium + blood vessels of urinary
system
--> All 3 pairs of kidneys
--> Everything EXCEPT primordial germ cells of genital system
--> Cortex of suprarenal gland

-Urogenital ridge: bulge between parietal and visceral LPM formed from proliferation of
intermediate mesoderm and covered by coelomic epithelium (urogenital mesentery)
-Nephrogenic cord --> urinary system
-Gonadal ridge --> genital system

-3 pairs of kidneys:
-Pronephros --> nephric duct (= part of mesonephric kidney’s drainage)
-Mesonephros --> Mesonephric (Wolffian) duct + Excretory tubules (some
become straight testis connecting rete testes+epididymis)
-Metanephros (definitive) --> Ureteric bud --> Metanephric cap/blastema
-Collecting part: Urogenetal sinus --> Ureteric bud --> Renal pelvis -->
Major calyces --> Minor calyces --> Collecting ducts
-Excretory part: Metanephric cap --> Renal vesicle --> Nephron
(Bowman’s capsule, PCT, Loop of Henle + DCT)
*Visceral LPM --> Glomeruli (capillaries in Bowman’s capsule)
-Kidneys initially supplied by initial “renal arteries”:
-Lateral sacral arteries
-Common iliac arteries
-Aortic bifurcation
-Aorta
-Fetal kidney functions to excrete any amniotic fluid swallowed by the fetus into the
amniotic cavity
-Definitive kidney filters some blood to produce very dilute urine
-Mature kidney’s function of excretion of waste is mainly performed by the
placenta

-Caudal mesonephric duct --> Ureteric bud --> Ureter --> Urogenital sinus
*Intermediate mesoderm forms lumen lining, CT and smooth muscles of the ureter

-Endodermally-lined cloaca --> Epithelium of urinary bladder

*Visceral LPM --> Muscular + serous walls of urinary bladder

-Upper part of urogenital sinus = urinary bladder = continuous with obliterated allantois -->
urachus --> median umbilical ligament

-Middle part of urogenital sinus = prostatic + membranous urethra in males

= entire urethra in females
-Last part of urogenital sinus = spongy urethra in males (+fusion of urethral folds)

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 = vestibule in females
-Mesonephric (Wolffian) duct --> Ductus deferens + Seminal vesicle --> Ejaculatory ducts
enter prostatic urethra

*Intermediate mesoderm --> Ejaculatory ducts

*Endoderm --> Urethra (males + females) and part of penis (also ectodermal)

-Intermediate mesoderm --> Outer cortex of suprarenal glands

-Neural crest cells --> Inner medulla of suprarenal glands

REPRODUCTIVE SYSTEM:
*Genital system begins to develop AFTER the urinary system

-Intermediate mesoderm --> Coelomic epithelium lining gonadal/genital ridge --> primitive
sex/cortical/testis cords --> medullary cords
--> CT + smooth muscle in genital ridge walls
-Primordial germ cells in epiblast --> Primitive streak --> Dorsal yolk sac wall -->
Gonadal ridges

-Indifferent gonads present in the indifferent stage of sexual development prior to

gametogenesis in week 7 have both sets of genital ducts = mesonephric + paramesonephric

-Development of testes:
-PGC enter and TDF induces seminiferous cords --> seminiferous tubules --> rete
testes --> efferent duct (from excretory tubules) --> mesopnephric (Wolffian) duct -->
epididymis --> ductus deferens --> ejaculatory duct + seminal gland --> enter
prostatic urethra running through prostate gland
-Mullerian inhibiting substance produced by sustentacular cells (intermediate
mesoderm) in seminiferous tubules prevents paramesonephric duct (uterus + uterine
tubes) from forming
-Tunica albuginea replaces the degenerated female cortical cords and separates
seminiferous cords from surface epithelium and rete testes
-Prostatic utricle is all that remains from the paramesonephric duct but is considered
vestigial
-Increased intra-abdominal pressure from organ growth and extra-abdominal
gubernaculum outgrowth pushes the testes through the process vaginalis (deep
inguinal ring --> inguinal canal --> scrotum)
-Process vaginalis is retained as tunica vaginalis
-Gubernaculum attaches to gonads proximally and genital swelling (external
genitalia) distally
-Distal portion of gubernaculum remains as scrotal ligament anchoring the
testes to the scrotum
-Testicular artery (from aorta) is retained and accompanies testis on their
descent

-Development of ovaries:
-Surface epithelium of ovaries divide to form cortical cords --> PGC enter and
undergo mitosis to form primordial follicles w/ follicular cells

22
 -Paramesonephric (Mullerian) duct --> uterine tubes, uterus, cervic + upper part of
vagina --> will open into abdominal area
-Lower part of vagina is formed from hollowing out part of urogenital sinus
(sinovaginal bulbs --> vaginal plate)
-Hymen separates lumen of vagina from urogenital sinus
-Gartner duct cysts are vestigial remnants of mesonephric (Wolffian) ducts located
between broad ligament and vagina
-Gubernaculum aids in ovary descent as well
-Superior part of gubernaculum becomes ovarian ligament proper
-Inferior part of gubernaculum becomes round ligament of uterus (attached
to the labium major)
-If process vaginalis persists after birth, it is called the canal of Nuck

-Intermediate mesoderm --> cloacal folds --> genital tubercle --> glans penis/clitoris
--> urethral folds --> labia minora
--> genital swellings --> scrotum/labia majora

Clinical Correlates

-Horseshoe kidney: lower kidney poles fuse and do not ascend higher than the inferior
mesentery artery

-Pancake kidney: congenital fusion of superior and inferior kidney poles, forming one mass
on the midline and preventing ascent past inferior mesentery artery

-Renal agenesis: lack of division of ureteric buds resulting in lack of development of

collecting ducts and nephrons can lead to one or both kidneys being absent (renal failure and
anuria leading to oligohydramnios and pulmonary hypoplasia)

-Hydronephrosis: dilatation of renal pelvis and calices due to obstructing in the urinary
passages

-Aberrant renal artery: accessory renal artery often forms on inferior kidney pole crossing
anterior to the ureter causing obstruction and hydronephrosis

-Double ureter: may or may not be associated with duplication of kidney next to median
umbilical artery

-Ectopic ureter: may open into vagina, urethra or vestibule due to faulty development of
mesonephric (Wolffian) duct

-Duplex ureter: splitting of ureteric bud causing duplication of the collecting part of the
kidney

-Ectopia vesicae/Extrophy of bladder: lumen of urinary bladder may be exposed on the

surface of the body and amniotic cavity due to the ventral body failing to close
*Associated with epispadias in males (urethra opens on dorsum of penis)

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-Congenital adrenal hyperplasia (CAH): due to excessive androgen production causing
masculization of external genitalia in females

-Cryptorchidism: testes fail to descend, thus unable to produce mature spermatozoa

-Ectopia: abnormal positions of testes under the skin of anywhere along the lower part of the
abdomen, thigh, in the femoral canal, penis, behind scrotum

-Agenisis: non-formation of testes

-Duplication: duplication of testes on ONE side

-Uterus didelphys w/ double vagina: lack of fusion of paramesonephric ducts throughout

the entire length

-Uterus arcuatus: lack of fusion of paramesonephric ducts at a small point (fundus)

-Uterus bicornis: lack of fusion of paramesonephric ducts but entering common vagina

-Uterus bicornis w/ 1 rudimentary horn: lack of fusion of paramesonephric ducts with

regression of 1 uterine horn

-Atresia of cervix: atresia of both distal ends of paramesonephric ducts leading to blockage

-Atresia of vagina: sinovaginal bulb does NOT develop

-Glandular hypospadias: external urethral orifice is on the ventral aspect of the glans penis
(w/ chordee, i.e. abnormal angle of head of penis)

-Penile hypospadias: external urethral orifice is on the ventral aspect of the glans penis (w/
chordee, i.e. abnormal angle of head of penis)

-Penoscrotal hypospadias: external urethral orifice is located at the penoscrotal junction

-Epispadias: external urethral orifice is on the dorsal surface of the penis

-Klinefelter syndrome: 47XXY = phenotypically male with infertility, impaired sexual

maturation + underandrogenization

-Gonadal dysgenesis: phenotypically female but may have XY karyotype = no oocytes +

malformed gonads

-Swyer syndrome: XY karyotype w/ female phenotype = deletion of SRY gene

resulting in no secondary sexual characteristics

-Turner syndrome: 45X = short stature +gonadal dysgenesis

-True hermaphrodites: 46XX = have both testes and ovaries (+ uterus)

24
-Pseudohermaphrodites: genotypic sex is masked by the phenotypic appearance of the
opposite sex but females have normal ovarian tissue and males have normal testicular tissue

-Testicular feminization/Androgen insensitivity syndrome: lack of androgen receptors

causes 46XY karyotype but with testes and female external genitalia and without uterus and
uterine tubes due to presence of Mullerian inhibiting substance

25
Development of Head & Neck

-Each pharyngeal arch consists of:

-Pharyngeal pouch (endoderm)
-Pharyngeal cleft/groove (ectoderm)
-Pharyngeal membrane lines cleft
-Mesenchymal core, which forms from:
-Neural crest cells --> CT, cartilage, bone + sensory neurons of
viscerocranium
-Lateral plate mesoderm --> Laryngeal cartilate + CT
-Paraxial mesoderm --> Neurocranium, craniofacial muscles + dermis
of dorsal head
-Ectodermal placodes + neural crest cells --> CN V, VII, IX, X

-Paraxial mesoderm + neural crest cells --> Membranous + Cartilagenous neurocranium

PHARYNGEAL ARCH 1:
-Pharyngeal arch 1 + neural crest cells --> Membranous viscerocranium
-Paraxial mesoderm of cranial somitomeres --> Skeletal muscle of arches 1-3
-Innervated by CN V
-Maxillary prominence --> Mastication, suprahyoid, tensor veli palatine (soft palate) +
tensor tympani muscles
-Mandibular prominence --> Maxilla, zygomatic + temporal bones
*Meckel’s cartilage --> Incus, malleus + spenomandibular ligament
-Forms anterior 2/3 of tongue via tuberculum impar (endodermal elevation)

PHARYNGEAL ARCH 2:
-Pharyngeal arches 2 + 3 --> Cartilagenous viscerocranium
-Paraxial mesoderm of cranial somitomeres --> Skeletal muscle of arches 1-3
-Innervated by CN VII
-Reichert’s cartilage --> Styloid process, stapes, most of hyoid + stylohyoid ligament
-Forms muscles of facial expression, posterior digastric, stylohyoid and stapedius muscles
-Forms taste buds and shares role with arches 3 + 4 in forming the posterior 1/3 of tongue
-Enlarges in week 5, overgrowing arches 3 + 4 and forming the cervical sinus

PHARYNGEAL ARCH 3:
-Pharyngeal arches 2 + 3 --> Cartilagenous viscerocranium
-Paraxial mesoderm of cranial somitomeres --> Skeletal muscle of arches 1-3
-Innervated by CN IX
-Forms rest of hyoid bone + stylopharyngeus muscle
-Forms taste buds and shares role with arches 2 + 4 in forming the posterior 1/3 of tongue

PHARYNGEAL ARCH 4 + 6:
-Pharyngeal arches 4 + 6 --> Thyroid + crycoid cartilage
-Paraxial mesoderm of occipital somites --> Skeletal muscle of arches 4 + 6

26
-Innervated by CN X (superior laryngeal branch for arch 4 + recurrent laryngeal branch for
arch 6)
-Form laryngeal cartilages + muscles, all soft palate (EXCEPT tensor veli palatine from arch
1) + pharyngeal muscles
-Arch 4 forms an epiglottic swelling and shares role with arches 2 + 3 in forming the
posterior 1/3 of tongue

-Skeletal muscles from pharyngeal arches --> Facial muscles, pharynx + larynx muscles
*Head & neck muscles NOT from pharyngeal arches (i.e. intrinsic muscles of the
tongue from occipital somites directly + extraocular eye muscles from somitomeres I-
IV directly)

-Formation of the face:

-Stomodeum (primitive mouth) is surrounded by a pair of maxillary and mandibular
processes as well as a frontonasal prominence
-Stomodeum is separated from the pharyngeal foregut by buccopharyngeal
membrane
-Ectoderm --> diverticulum --> Rathke’s pouch --> anterior + intermediate
lobes of the pituitary gland
-Infundibulum --> posterior lobe of pituitary gland
-2 nasal placodes (ectoderm) form on both sides of the frontonasal process
--> nasal (olfactory) pits --> future nasal cavities
-Nasal pits surrounded by lateral and medial nasal prominences
-Oronasal membrane ruptures and forms the primitive choana
-Nasal septum grows downwards and unites with 2 palatine shelves to form
separate R and L nasal chambers
-Nasal placode tissue --> Primary sensory olfactory epithelium
*Joins with secondary neurons of olfactory bulbs
-Lens placodes --> lens of eye
-Ear will form between pharyngeal arches 1 + 2
-Frontonasal prominences --> forehead, bridge of nose + nasal septum
-Fusion of maxillary prominences + medial nasal prominences --> intermaxillary
segment (primary hard palate) + nasolacrimal groove + crest/tip of nose
-Fusion of maxillary prominences --> upper lip, cheeks + secondary hard
palate from palatine processes
*Secondary palate, primary palate and nasal septum fuse by
intramembranous ossification of neural crest cells from maxillary
prominence
-Lateral nasal prominences --> ala of nose
-Mandibular prominences --> chin, lower lip + lower cheeks
*Ectoderm --> Lip region (maxillary + mandibular prominences)
-Endoderm --> Inner oral cavity (GI tube)

-Pharyngeal pouches (endoderm) + clefts (ectoderm) --> Epithelial components of lymphoid

+ endocrine glands
-1st pouch --> Epithelial lining of middle + outer ear, tympanic membrane +
pharyngotympanic tube
-1st cleft --> external auditory meatus in adults
-2nd pouch --> Epithelial lining of palatine tonsil

27
 -2nd cleft --> NO structures
rd
-3 pouch + cleft --> Epithelial components of thymus gland + inferior parathyroid
gland
-4th pouch --> Superior parathyroid gland
-4th cleft --> NO strucures
-5th pouch --> Parafollicular cells of the thyroid (merge w/ 4th pouch)

-Mesoderm + neural crest cells in pharyngeal arches --> Rest of organs

Clinical Correlates

-Cleft lip: medial nasal prominences do not fuse with maxillary prominences

-Cleft palate: secondary palates do not fuse with each other with primary palate

-Cleft lip + palate: non-fusion extends to maxilla (between primary and secondary palates)
-Median clefted upper lip: 2 medial nasal prominences fail to fuse (w/ mental retardation)

-Oblique facial cleft: nasolacrimal duct remains exposed due to the lateral nasal process
failing to fuse with the maxillary process (w/ cleft lip)

-Bifid tongue: midline split in anterior 2/3 of tongue due to improper fusion of the lateral
lingual swellings at median sulcus

28
Development of the Nervous System & Special Senses (Eye + Ear)

-Medial ectoderm --> neuroectoderm --> neural plates + groove --> neural folds
-Fusion of neural folds leave 2 open ends = neuropores
-Neuroepithelial cells --> Neuroblasts
--> Glioblasts --> glia in CNS from neural tube
(astrocytes, oligodendrocytes + radial cells)
--> glia in PNS from neural crest cells
(Schwann, satellite + enteric cells)
-Neuroepithelial cells line central canal of spinal cord
-Those that do not migrate into the canal and produce CSF become ependymal cells
-Mesenchyme --> microglia (invade neural tube to ingest and remove cellular debris)
-Cranial end of neural tube expands to 3 dilations/primary brain vesicles:
1. Prosencephalon (forebrain) --> Telencephalon --> primitive cerebral hemispheres
--> Diencephalon --> outgrowth of optic vesicles,
(CN II) thalamus, hypothalamus +
pituitary gland (from alar plate)
*2 additional neuronal layers in cerebral cortex, similar to cerebellum
-Mesoderm --> dura mater
-Mesoderm + neural crest cells --> arachnoid mater + pia mater
-----------------------------------------------------------------------------------CEPHALIC FLEXURE
2. Mesencephalon --> midbrain (CN III + IV)
*Alar region --> superior + inferior colliculi (sensory relay nuclei for auditory
and visual systems to cerebral cortex)
*Basal region --> motor fibers tracks from cerebral cortex to cerebellum +
spinal cord
---------------------------------------------------------------------RHOMBENCEPHALIC ISTHMUS
3. Rhombencephalon (hindbrain) --> Metencephalon --> pons + cerebellum
(CN VIII)
*Alar plates --> cerebellar hemispheres
*Basal plates --> everything else
-------------------------------------------------------------------------------------PONTINE FLEXURE
--> Myencephalon --> medulla oblongata
(CN IV, IX, X, XI, XII)
*3 additional layers = Granula, Purkinje + Molecular layers
-----------------------------------------------------------------------------------CERVICAL FLEXURE

-3 different layers form across neural tube:

1. Ventricular/ependymal zone (germinal mitotic layer, gives rise to 2 other layers)
2. Intermediate/mantle zone (gray matter of CNS) --> Alar (dorsal) region = sensory
--> Basal (ventral) region = motor
*Alar and basal plates shift due to enlargement/contraction of ventricles
3. Marginal zone (white matter of CNS)

29
-Most of brain retains these 3 layers but the cerebral cortex gains 2 additional layers (gray
matter cell bodies)
-Cross section width of spinal cord varies due to cervical and lumbar mattle zone
enlargement innervation of upper and lower limbs as well as decreasing fiber tracts in white
marginal zone at caudal end of spinal cord
EYE:
-Optic grooves --> optic vesicles --> optic cup --> lens placode --> lens vesicle (ectoderm)
+ optic stalk (--> optic nerve)
w/ choroid fissure (hyaloid artery enters here)
-Lumen of optic vesicle is reduced to a slit between:
-Inner neural layer
-Intraretinal space
-Outer pigment layer of the optic cup
-Mesenchyme around the optic vesicle --> sclera (fibrous coat)
--> cornea (fibrous coat)
--> choroid layer
--> hyaloid vessels (hyaloid artery --> central artery)
--> vitreous body (between lens and inner wall of
optic cup, passes through choroid fissure to supply
lens)
-Neural crest cells --> sphincter + dilator pupillae muscles of ciliary body + iris
--> substantia propria of cornea + posterior corneal endothelium
-Lateral plate mesoderm --> stroma, ciliary muscle + suspensory ligament of ciliary body
--> stroma of iris
-Surface ectoderm --> lens
--> anterior corneal epithelium
--> eyelids, conjunctiva, lacrimal gland, nasolacrimal duct + lacrimal sac
-Paraxial mesoderm (cranial to occipital somitomeres I-IV) --> extraocular muscles

EAR:
-Pharyngeal arch 1 --> external acoustic meatus
*Filled with ectodermal cells forming a meatal plug that disintegrates after birth
-1st pouch --> pharyngotympanic tube + tympanic cavity
-1st cleft --> tympanic membrane
-Pharyngeal arches 1 + 2 --> 6 auricular swellings --> auricle
--> middle ear ossicles (malleus + incus from arch 1 and stapes
from arch 2)
*Ossicles attach to tympanic cavity by endoderm
--> otic placode --> otic vesicle --> utricle (dorsal part)
--> saccule (ventral part)
of membranous labyrinth

30