EARLY EMBRYOLOGY: SOMITE STAGE AND LIMB BUDS

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Week 1-2: formation of zygote, implantation and formation of bilaminar embryo (p. 3-4, fig. 1-1). Weeks 3-8: Embryological period (p. 4-5, fig. 1-1). Weeks 9-38: Fetal period (p. 5-6, figs. 1-1 and 1-2).

DEVELOPMENT OF THE SOMITES (week 3) The intraembryonic mesoderm on each side of the forming notochord and neural tube thickens to form a longitudinal column of paraxial mesoderm. By the end of the 3rd week, the paraxial mesoderm divides into paired bodies called somites, located bilaterally of the neural tube (p. 64, fig. 4-10). Somites
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The somites give rise to the axial skeleton (vertebrae, ribs), associated musculature and adjacent dermis of skin. The first pair of somites develop a short distance posterior to the cranial end of the notochord, and the rest of the somites form caudally. Around 38 pairs of somites form during the somite period of development, from days 20 to 30. The final number is 42 to 44 pairs. The somites may be used as a criterion to determine the age of the embryo (p. 81-89). A cavity, the mycocoele, forms within each somite but disappears. Each somite becomes differentiated into ventromedial sclerotome (for vertebrae and ribs), myotome (muscles) and dermatome (skin; p. 340, fig. 141).

Week 4
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At the beginning of the 4th week, the somites (4) are well formed and the neural tube is also formed but it is opened at the rostral and caudal neuropores (p. 81, fig. 5.8). Upper limb buds become recognizable during week 4 (day 26 or 27) and the lower limb buds become present by the end of week 4 (day 28; p. 84, fig. 5.12). The patterning of the limb development is regulated by Homeoboxcontaining (Hox) genes. The upper limb buds appear low on the embryo due to the dominant development of the head and neck. The upper limb buds form opposite the caudal cervical segments and lower limb buds form opposite the lumbar and upper sacral segments.

Limb bud (p. 366, fig. 16-2) Each limb bud consists of a mass of mesenchyme derived from the somatic mesoderm, covered by a layer of ectoderm. At the tip of each limb bud, ectodermal cells form an apical ectodermal ridge, which promotes growth and development of the limbs in the proximo-distal axis . Fibroblast growth factors and T-box genes (tbx-4 and tbx-5) from the apical ectodermal ridge activate the mesenchymal cells at the posterior margin of the limb bud (the zone of polarizing activity). This causes expression of the Sonic Hedgehog gene, which controls the patterning of the limb along the anterior-posterior axis. Expression of Wnt7 from the dorsal epidermis of the limb bud and engrailed-1 (EN-1) from the ventral aspect specifies the dorsal-ventral axis Week 5
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Bones appear during week 5 as mesenchymal condensations in the limb buds (p. 371, fig. 16-7) Upper limbs show regional differentiation with developing hand plates (p. 367, fig. 16-3).

Week 6 (p. 354, fig. 14-14; p. 371, fig. 16-7)
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Mesenchymal models of the bones in the limbs undergo chondrification to form hyaline cartilage. The clavicle develops by intramembranous ossification and later develops articular cartilages. The cartilage models form sooner in the upper limb than in the lower limb and in a proximodistal sequence.

Further differentiation of the limb buds during week 6 (p. 367, fig. 16-3):
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Identifiable elbow and wrists regions are formed. Hand plates develop ridges, called digital rays and these will become the future thumb and fingers. At the tip of each digital ray is a portion of the apical ectodermal ridge. It induces development of the mesenchyme into the primordia of bones. Areas between the rays contain loose mesenchyme. Development of the lower limb buds is always slower by a few days.

Week 7
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Loose mesenchyme between the digital rays break down and notches appear between the digital rays in the hand plates.

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Digital rays form in the foot plate. Ossification in the long bones begin by the end of the embryonic period (week 7). The primary centers are in the diaphyses (p. 343, fig. 14-5). Limb muscles are formed by myogenic precursor cells that migrate into the limb buds and differentiate into myoblasts. They are derived from the dorsolateral muscle-forming region of the somites, an area which expresses the muscle-specific genes MyoD and myf-5. Expression of MyoD results from the influence of activating Wnt proteins and inhibitory BMP-4 protein. The myoblasts form a muscle mass which divides into a dorsal (extensor) and ventral (flexor) compartments.

Limb rotation begins (p. 373, fig. 16-9):
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Originally, the flexor aspect of the limbs is ventral and the extensor aspect is dorsal; the preaxial border is cranial and the postaxial border is caudal in direction. The upper limbs rotate 90 degrees on their longitudinal axis. Elbows point posteriorly and extensor muscles now lie lateral and posterior. The lower limbs rotate 90 degrees in the opposite direction of rotation of the upper limbs and the knees face anteriorly. The extensor muscles now lie anteriorly. The radius in the forearm is homologous to the tibia in the leg, and the ulna is homologous to the fibula. Muscles of the limb shift their position during development because of the lateral rotation of the upper limb and medial rotation of the lower limb. Muscles forming on the dorsal side of the long bones give rise to extensor and supinator muscles of the upper limbs and extensor and abductor muscles of the lower limb. They are innervated by the dorsal branches of the ventral primary rami. Muscles forming on the ventral side of the long bones become flexor and pronator muscles of the upper limb and flexor and adductor muscles of the lower limb. They are innervated by the ventral branches of the ventral primary rami.

Week 8 (Last week of embryonic life; p. 372 fig. 16.8) At the beginning of week 8,
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The digits of the hand are short and webbed. Notches develop between the digital rays of the feet.

fig.. 16-10).At the end of week 8. fig. As the limbs elongate. Order of ossification: Clavicle. The distribution is segmental. Initially. 5-6. the upper limbs have reached their final relative length but the lower limbs have not. Development of the innervation of the limbs y y y y Peripheral nerves grow from the brachial and lumbar plexuses into the mesenchyme of the limb buds during week 5. 1-1 and 1-2) Weeks 9-12 y y y y The fetus has short legs and small thighs at the beginning of week 9. Development of the blood supply to the limbs Limb buds are supplied by branches of the intersegmental arteries arising from the aorta (p. The first ones to appear are in the distal end of the femur and the proximal end of the tibia. 16-11). fig. A dermatome is the area of skin innervated by a single spinal nerve and its dorsal root ganglion (p. a primary axial artery and its branches supply the limb bud and a peripheral marginal sinus drains it. 343. In the upper limb. 343. 374. at the knee joint. supplying both dorsal and ventral aspects. By the end of week 12. FETAL PERIOD (p. growth of the bones ends. 14-5). there are distinct regions in the limbs.. fig. 373. with long fingers and distinct toes. . Primary ossification centers are present in all long bones (p. the cutaneous distribution follows and an orderly sequence can still be seen in the adult. 14-5). The epiphyseal cartilage plate intervenes between the diaphysis and epiphysis. fig. femora. Weeks 34-38 y y Secondary ossification centers appear in the epiphyses (p. etc. When it is replaced around age 25. There is no overlap across the axial line.

1. and the anterior and posterior tibial arteries in the leg. surrounding the neural tube. p. 8th ed. In the lower limb. The final pattern of basilic and cephalic veins and their tributaries then arises. o The terminal branches of the brachial artery are the radial and ulnar arteries.y y The primary axial artery becomes the brachial artery in the arm and the common interosseous artery in the forearm. With the formation of the digits the marginal sinus breaks up into the dorsal venous arch. mesenchymal cells from the sclerotome of the somites are found in 3 main areas (The Developing Human. in the body wall. Around the notochord .. updated 8/25/2008 Embryology of the spine and spinal cord The AXIAL SKELETON is formed by the : y y y y VERTEBRAL COLUMN 12 PAIRS OF RIBS STERNUM SKULL Development of the vertebral column Precartilaginous (mesenchymal) stage During week 4. y The primary axial artery will form the profunda femoris artery in the thigh. o The terminal branches of the common interosseous arteries are the anterior and posterior interosseous arteries. 345): y y y around the notochord.

.  Each centrum thus develops from 2 adjacent sclerotomes and becomes an intersegmental structure (The Developing Human. p. 2. 345). Surrounding the neural tube These mesenchymal cells form the vertebral arch (The Developing Human. The nucleus pulposus is later surrounded by the circular fibers of the anulus fibrosus. Peripheral nerves will form close to the intervertebral discs. 8th ed. the dorsal intersegmental arteries become the intercostal arteries. 345) o o o Some densely packed cells move cranially and form the intervertebral disc. The remaining densely packed cells fuse with the loosely arranged cells of the adjacent caudal sclerotome and form the mesenchymal centrum of the vertebra. the notochord expands to form the nucleus pulposus (The Developing Human. Intersegmental arteries will come to lie on each side of the vertebral bodies. The notochord degenerates and disappears where it is surrounded by the vertebral body. 345). p. The nucleus pulposus and anulus fibrosus form the intervertebral disc. This slow-growing neoplasm occurs most frequently at the base of the skull and in the lumbosacral region (arrows in scans below) . 8th ed.. In the body wall These mesenchymal cells form the costal processes which develop into ribs in the thoracic region.. 8th ed. The cartilaginous stage . 8th ed. o o o o Between the vertebrae. 3. p.. p. Remnants of the notochord may persist and give rise to a chordoma.Each sclerotome consists of loosely packed cells cranially and densely packed cells caudally (The Developing Human. In the thorax. 345).

The bony stage Ossification of the typical vertebrae begins during the embryonic period and ends by year 25 of life.. each vertebra consists of 3 bony parts connected by cartilage (The Developing Human. Prenatal period 2 (ventral and dorsal) primary ossification centers for the centrum fuse to form one. At birth. p. 346): o o in the centrum. These articulations permit the vertebral arches to grow as the spinal cord enlarges. chondrification centers appear in each mesenchymal vertebra (The Developing Human. 3 primary ossification centers at the end of the embryonic period (The Developing Human. the centers in the vertebral arches fuse with each other and with the centrum. o o o The 2 centers in each centrum fuse at the end of the embryonic period to form a cartilaginous centrum... 346). The neurocentral joints disappear when the vertebral arch fuses with the centrum during years 3-6.. 8th ed.During week 6. The spinous and transverse processes develop from extensions of chondrification centers in the vertebral arch. At the same time. p. The laminae of the arch first unite in the lumbar region and the progression moves cranially. 346). p. The vertebral arch articulates with the centrum at cartilaginous neurocentral joints (The Developing Human. 8th ed. 8th ed. Postnatal period The halves of the vertebral arch fuse during years 3-5. 346). 8th ed. Chondrification spreads until a cartilaginous vertebral column is formed. in each half of the vertebral arch (Ossification is evident around week 8). p. .

The neural crest gives rise to the peripheral nervous system (cranial. The Developing Human. 12 T. p. 8th ed. 2 rim (annular) epiphyses: 1 superior and 1 inferior for the vertebral body. C7. It includes the centrum. tip for each transverse process. All secondary centers unite with the rest of the vertebra around year 25. y y The neural tube gives rise to the central nervous system (brain and spinal cord. 2% have 1 less... The underlying notochord and adjacent mesoderm induce the formation of the neural plate.After puberty 5 secondary ossification centers appear (The Developing Human. o o o 95% of the population has 7C. 8th ed. 382). pigment . sacrum and coccyx. Ossification of atypical vertebrae Exceptions to the typical ossification of vertebrae occur in C1.. 8th ed. parts of the vertebral arch and the facets for the heads of the ribs. lumbar vertebrae. 346): o o o tip of the spinous process. Development of the spinal cord The nervous system develops from an area of embryonic ectoderm called the neural plate which appears during week 3 (The Developing Human. autonomic ganglia and nerves) and Schwann cells. C2. 3% have 1 or 2 more vertebrae. p. 396). The vertebral body is a composite of the superior and inferior annular epiphyses and the mass of bone between them. The neural tube and the neural crest differentiate from the neural plate. peripheral. Examine the entire vertebral column because an apparent extra or absent vertebra in one segment may be compensated by an absent or extra vertebra in an adjacent segment (ex: 11T and 6 L vertebrae). p. 5 L and 5 S vertebrae.

Neural folds fuse and the neural tube is temporarily open at both ends. meninges. and bones and muscles of the head (The Developing Human.cells. 8th ed. 8th ed. 386.the cranial 2/3 of the neural plate and neural tube down to somites #4 represent the brain and the caudal 1/3 of the neural tube and plate represent the spinal cord. The lumen of the neural tube is converted to the ventricular system of the brain and the central canal of the spinal cord. The remaining neuroepithelial cells differentiate into ependymal cells lining the central canal of the spinal cord (The Developing Human. columnar neuroepithelium in the walls constitute the ventricular zone (ependymal layer) and give rise to all neurons and macroglial cells (astroglia and oligodendroglia) in the spinal cord (The Developing Human. The rostral neuropore closes around day 25 and caudal neuropore on day 27.. Neuroepithelial cells in the ventricular zone differentiate into neuroblasts and form an intermediate zone between the ventricular and marginal zones. y y y y y The central canal is formed by week 9 or 10 (The Developing Human. 386). Pseudostratified. spinal ganglia and brain. .384) At this stage . p. Walls of the neural tube thicken to form the brain and spinal cord. They will give rise to neurons... 8th ed. 387). They migrate from the ventricular zone into the intermediate and marginal zones.. odontoblasts. Others become oligodendroblasts and then oligodendroglia (oligodendrocytes). 8th ed. The Developing Human. communicating freely with the amniotic cavity.. Some become astroblasts and then astroglia (astrocytes). p. p. 389). p. The outer parts of the neuroepithelial cells differentiate into a marginal zone which will give rise to the white matter of the spinal cord as axons grow into it from neurons in the spinal cord. 8th ed. 388). 382. Central nervous system y y y y y y Formation of the neural tube begins during the early part of week 4 (22-23 days) in the region of the 4th to 6th pairs of somites (future cervical region of the spinal cord. p. Glioblasts (spongioblasts) differentiate from neuroepithelial cells after neuroblast formation has stopped. The spinal cord is formed from the neural tube caudal to somites 4. 382.

y Microglia are derived from the mesenchymal cells. y y The outer layer thickens to form the dura mater. 390) y y y At month 6 of gestation. In the newborn infant. They invade the nervous system late in the fetal period after penetration from blood vessels. y y y Alar plates: cells form the dorsal horns and will have afferent functions. Positional changes of the developing spinal cord In the embryo. the end of the spinal cord lies at the level of S1. The dorsal root ganglia are formed from the neural crest cells. Basal plates: cells form the ventral and lateral horns and will have efferent functions. A shallow longitudinal sulcus limitans appears in the lateral walls of the spinal cord and separates the dorsal alar plate from the ventral basal plate (The Developing Human. Axons grow out of the spinal cord to form the ventral roots. Mesenchyme surrounding the neural tube condenses to form the primitive meninx. dorsal muscles and skin). Their axons enter the spinal cord and form the dorsal roots. 8th ed. 8th ed. This relationship does not persist because the spine and the dura mater grow more rapidly than the spinal cord. .. Congenital malformations: y are mostly due to the defective closure of the caudal neuropore at the end of week 4. Positional changes of the developing spinal cord (The Developing Human.. p. p. vertebral arch. it lies at L 2-3. 386). the spinal cord extends the entire length of the vertebral canal and the spinal nerves pass through the intervertebral foramina near their levels of origin. The caudal end of the spinal cord comes to lie at relatively higher levels. it lies at L 3 In the adult. The inner layer remains thin and forms the pia-arachnoid. The defects will involve the tissue overlying the spinal cord (meninges. Lumbar and sacral spinal nerve roots run obliquely from the spinal cord to their corresponding intervertebral foramina inferiorly. Proliferation and differentiation of the neuroepithelial cells in the developing spinal cord produce thick walls and thin roof and floor plates.

complete or partial skeletal muscle paralysis. p. It is the last place of separation between the ectoderm and the neural tube. Spina bifida y y y with meningocele: only meninges and cerebrospinal fluid in the sac. may result in loss of sensation in corresponding dermatome. 391. 8th ed. There are marked neurological deficits inferior to the sac. may only be evident as a small dimple with a tuft of hair. p. . p. occurs at L 5 or S 1 vertebra in about 10% of the population. The spinal cord in this area is a flattened mass. Spina bifida cystica (The Developing Human. produces no clinical symptoms although a small percentage may have significant defects of the underlying spinal cord and spinal roots.y involving the spinal cord and vertebral arches are called spina bifida (nonfusion of the vertebral arches. 391) Spina bifida occulta (The Developing Human.. sphincter paralysis (with lumbar meningomyeloceles) and saddle anesthesia. 8th ed.. Intramedullary dermoids are tumors arising from surface ectodermal cells incorporated into the neural tube during closure of the caudal neuropore. 8th ed. The dimple may be connected by a fibrous cord with the dura mater. due to incorporation of the neural tissue into the wall of the sac (This usually occurs in the lumbar region and may be associated with craniolacunia or defective calvarium). p. may exist. The Developing Human. 392 fig. 393) y y y is a protrusion of the spinal cord and/or meninges through the defective neural arch. covered by skin or thin membrane.. 17-14) y y y y is a defect in the vertebral arch (neural arch) resulting from failure of the halves of the vertebral arch to grow normally and fuse in the median plane. Spinal dermal sinus y y y representing the area of closure of the caudal neuropore at the end of week 4. 391. with myeloschisis (with myelocele: open spinal cord due to failure of neural folds to fuse. 393): spinal cord and nerve roots included with meninges and CSF in the sac. 8th ed. with meningomyelocele (The Developing Human. is present in 1/1000 births..

8th ed.. The endoderm (The Developing Human. p. o Amniocentesis or ultrasound should be performed at about week 10 when the vertebral column becomes visible. A fistula (The Developing Human. In a newborn infant. updated 9/8/2008 RESPIRATORY EMBRYOLOGY The lower respiratory system (from the pharynx down) y y y y develops during week 4 (26-27 days) starts as a median laryngotracheal groove (The Developing Human. 8th ed.y cystica and/or meroanencephaly (absence of part of the brain. The laryngotracheal groove deepens into a diverticulum ventrally which enlarges distally into a lung bud (The Developing Human. bronchi and the pulmonary epithelium. p. p. y y This is usually associated with superior esophageal atresia.. Gastric contents may reflux into the trachea and lungs resulting in pneumonia or pneumonitis (inflammation of the lungs). 200. 201. dividing the foregut into the ventral laryngotracheal tube and the dorsal esophagus. (The Developing Human. 395) is suspected in utero when there is a high-level of alpha-fetoprotein in the amniotic fluid or in the maternal blood serum. 10-3) in the caudoventral wall of the primitive pharynx. cartilage and smooth muscle of these structures develop from the splanchnic mesenchyme surrounding the foregut. p. 392.. fig. p. 200. . fig. 10-2). 10-5. 10-6) may exist connecting trachea and esophagus and resulting in abnormal communication between the 2.. The diverticulum becomes separated from the primitive pharynx by longitudinal trachoesophageal folds which fuse to form the trachoesophageal septum. 202. 8th ed. 10-4) lining the groove gives rise to the epithelium and glands of the larynx. 8th ed. fig. fig.. this is associated with coughing and choking upon swallowing. 8th ed. Connective tissue. trachea. An excess of amniotic fluid (polyhydramnios) is associated with esophageal atresia and trachoesophageal fistula because amniotic fluid may not pass to the stomach and intestines for absorption and transfer via the placenta for disposal.

fig. The right one is slightly larger than the left and is oriented more vertically (The Developing Human. p.. fig. They will divide an additional 7 more times before birth. 8th ed.. p. 8th ed. although the chances of survival are slim. p. As the bronchi develop. they divide another 14 times and the respiratory bronchioles have developed. 3) Terminal sac period (24 weeks to birth) y y More terminal sacs develop and capillaries enter into close relationship with them. 204. respiratory bronchioles have developed and respiration becomes possible. the primordia of the pleural cavities. 10-7) y y The lungs acquire a layer of visceral pleura from the splanchnic mesenchyme. PLEURAE (The Developing Human. smooth muscle.. p. 8th ed. y y y y y Early in week 5. connective tissue and capillaries. 205. the surrounding mesenchyme synthesizes the surrounding cartilages. 202. 10-8. No respiration is possible! 2) Canalicular period (16-25 weeks) The lumen of the bronchi and terminal bronchioles become larger and the lungs become vascularized. 8th ed. 10-10) 1) Pseudoglandular period (5-17 weeks) By week 17 all major elements of the lungs have formed except for those involved with gas exchange. fig. Type II pneumocytes secrete surfactant counteracting the surface tension forces and facilitating expansions of the terminal sacs. fig. The thoracic body wall becomes lined by a layer of parietal pleura derived from the somatic mesoderm. The lungs look like an endocrine organ.The lung bud develops into 2 endodermal bronchial buds (The Developing Human.. The primary bronchi subsequently divide into secondary bronchi and then into the tertiary bronchi by week 7. p. . 203. 202. fig. They are lined with Type 1 alveolar cells or pneumocytes. each bronchial bud enlarges into the primordium of a primary bronchus. By week 24. By week 24. 10-9. LUNG DEVELOPMENT (The Developing Human. 10-7) which grow into the pericardioperitoneal cavities.

into the lymphatics and pulmonary arteries and veins. Mesenchymal cells derived from the mesoderm form endothelial tubes which join to form the primitive vascular system (The Developing Human. fig.. Bilateral cardiogenic cords y y y are formed from the mesenchyme become canalized and form the paired endocardial heart tubes (The Developing Human. p. A newborn infant has only 1/6 to 1/8 of the adult number of alveoli and the lungs look denser in an x-ray. 8th ed. Developing lungs at birth are half filled with amnotic fluid. Surrounding mesenchyme thicken to form the myoepicardial mantle (future myocardium and epicardium) separated from the endothelial heart tube (future . 13-8). Adequate pulmonary vasculature and sufficient surfactant are critical to the survival of premature infants.. 13-7. 8th ed. 286. 131). HEART DEVELOPMENT (WEEK 3) Heart develops from splanchnic mesenchyme in the cardiogenic area. updated 9/14/2008 CARDIOVASCULAR EMBRYOLOGY The cardiovascular system begins to develop during week 3. The fluids in the lungs are cleared: y y y through mouth and nose by pressure on the thorax during delivery. 4) Alveolar period (late fetal period to 8 years) 95% of the mature alveoli develop after birth. into the pulmonary capillaries. 294 fig. p. These fuse into a single heart tube forming the primitive heart.Surfactant reaches adequate levels 2 weeks before birth. 293. fig. p.

. 13-8 E).. 8th ed.. p. The bulbus cordis and the ventricle grow faster and the heart bends upon itself. p. 8th ed. 8th ed. p. p. p. fig. 13-8). 13-8). p. p.. 13-10). 295). The sinus venosus receives (The Developing Human. 290). the cardinal veins will become the caval system. fig. forming a bulboventricular loop (The Developing Human. p. 289. 8th ed. . 13-10): y y y the umbilical veins from the chorion. fig. fig. 296. 3 systems of paired veins drain into the primitive heart: y y y the vitelline system will become the portal system. The atrium and sinus venosus come to lie dorsal to the bulbus cordis. 297).. 294. The future heart develops dilatations and constrictions resulting in 4 chambers (The Developing Human. 8th ed. 8th ed. 294. 294. 8th ed. and enlarges cranially to form the aortic sac from which the aortic arches arise (The Developing Human. 287. the heart invaginates into the pericardial cavity (The Developing Human. 8th ed.. the vitelline veins from the yolk sac the common cardinal veins from the embryo.. 296-298): y y y y sinus venosus primordial atrium ventricle bulbus cordis The truncus arteriosus is continuous caudally with the bulbus cordis. p. truncus arteriosus and ventricle (The Developing Human.endocardium) by the gelatinous cardiac jelly (The Developing Human. The dorsal mesocardium which attaches it to the dorsal wall of the pericardial cavity degenerates and forms the tranverse pericardial sinus (The Developing Human. fig.. the umbilical system which degenerates after birth (The Developing Human. 8th ed.. 296. At the same time.

8th ed. 8th ed. The latter is an incomplete partition and leaves a foramen ovale. dividing the atrioventricular canal into right and left canals. Blood then passes to the dorsal aortae for distribution to the embryo.. 4) The primitive pulmonary vein and its 4 main branches become partially incorporated into the left atrium (The Developing Human. 287) and branchial arches. 1) Endocardial cushions (The Developing Human. The foramen ovale has a valve formed from the degeneration of the cranial portion of the septum primum. yolk sac and placenta.. forming peristalsis-like waves beginning in the sinus venosus. p. At week 5.First heartbeat occurs at 21 to 22 days and originates in the muscle. Blood flows into the primitive ventricle. is derived from the sinus venosus whereas the muscular part.. 302) and a right horn which will be incorporated into the right atrium. The heart divides into 4-chambered heart between weeks 4 and 7. blood flows into the bulbus cordis and the truncus arteriosus into the aortic sac.. After birth the foramen ovale normally closes by fusion of the septum primum and the septum secundum. The 2 portions are separated internally by the crista terminalis and externally by the sulcus terminalis. This . 8th ed. passing into the aortic arches (The Developing Human. 287). 8th ed. p. 299-301). is derived from the primitive atrium. cardinal and umbilical veins (The Developing Human. Upon ventricular contraction. 301).. By the end of week 4 coordinated contractions of the heart results in unidirectional flow: y y y y Blood enters the sinus venosus from the vitelline. 8th ed. 8th ed. p. p. 303).. reflux is prevented by the valve (The Developing Human. p. 3) The sinus venosus develops a left horn which becomes the coronary sinus (The Developing Human. 8th ed. Before birth the foramen ovale allows blood to pass from the right atrium into the left atrium. the sinus venarum. p. 2) Atria are partitioned successively by the septum primum and the septum secundum (The Developing Human. they approach each other and fuse. 297-298) form on the dorsal and ventral walls of the atrioventricular canal. the auricle. p.. The smooth part of the right atrium.

It is part of the sinus venosus which becomes incorporated into the right atrium. The primitive atrium acts as a temporary pacemaker. 307. 313) which fails to develop. But the sinus venosus soon takes over.. 5) The ventricles become partitioned by a crescentic fold which is open cranially until the end of week 7 (interventricular foramen. . The portion derived from the original left atrium retains a trabeculated apperance.results in the 4 pulmonary veins. y y The sinuatrial (SA) node develops during week 5. p. 304). Membranous ventricular septal defect (most common): y y involves the oval membranous portion of the interventricular septum (The Developing Human. The critical period of development is from day 20 to day 50 after fertilization. is due to the failure of extensions of subendocardial tissue growing from the right side of the fused endocardial cushions and fusing with the aorticopulmonary septum and the muscular part of the interventricular septum. The interventricular septum is formed of a central membranous part and a surrounding muscular part. p. Muscular septal defect: y Perforation may appear anywhere in the muscular part of the interventricular septum (multiple defects = Swiss cheese type of ventricular septal defect) due perhaps to excessive resorption of myocardial tissue during formation of the muscular part of the interventricular septum. the right ventricle communicates with the pulmonary trunk and the left ventricle with the aorta. Improper partitioning of the heart may result in defects of the cardiac septa. 304. p. 317). The atrioventricular (AV) node also develops from the cells in the wall of the sinus venosus together with cells from the atrioventricular canal region.. the bulbus cordis and the truncus arteriosus become divided by an aorticopulmonary septum into the definitive pulmonary trunk and aorta (The Developing Human. Valves develop from proliferation of the subendocardial tissue. of which the ventricular septal defects are most common (25% of congenital heart disease). 6) During week 5. 8th ed. After closure.. The Developing Human. 8th ed. 8th ed.

Most of the blood in the right atrium passes through the foramen ovale into the left atrium and mixes with the blood returning from the lungs (deoxygenated). lymph nodules do not appear until just before and/or after birth.. 334). Aortic arches y y When the branchial arches form during week 4 and 5. 8th ed. p. The lymphatic system begins to develop around week 5 (The Developing Human. y y y 6 primary lymph sacs develop and later become interconnected by lymph vessels. p. Blood enters into the inferior vena cava and then the right atrium of the heart. and pulmonary arteries (The Developing Human. p. subclavian. p. ventricular septal defect overriding aorta hypertrophy of right ventricle Cyanosis is an obvious sign but may not be present at birth. This blood is now partially deoxygenated because it is mixed with returning blood from the lower portion of the body and the abdominal organs.Absence of interventricular septum is rare and results in a 3-chambered heart called cor triloculare biatriatum. 321). 8th ed. During week 6 to 8 the primitive aortic arch pattern is transformed into the adult arterial arrangement of carotid. The tetralogy of Fallot consists of (The Developing Human. .. which are called the aortic arches. Half of the blood passes through the liver whereas the other half bypasses the liver by the ductus venosus. Hygroma: tumor-like mass of dilated lymphatic vessels derived from the pinched-off portion of the jugular lymph sac. 316): y y y y pulmonary valve stenosis: the cusps of pulmonary valve are fused together to form a dome with a narrow central opening. FETAL CIRCULATION (The Developing Human. they are penetrated by arteries arising from the aortic sac... 328-329) y y y y Oxygenated blood returns from the placenta by the umbilical vein. 8th ed. 8th ed.

p. 8-2C). the left ventricular wall is thicker. bypassing the lungs. It passes into the right ventricle and leaves via the pulmonary trunk. 8-2B) and its lateral limbs represent the future pleural and peritoneal cavities (fig.y y y From the left atrium. 8th ed. the foramen ovale. . 333). 50% of the blood passes via the umbilical arteries into the placenta for reoxygenation... The right ventricular wall is thicker in the newborn but by the end of month 1. fig. p. 8-1). 8th edition Chapter 8 The intraembryonic coelom is the primordium of the embryonic body cavities and begins to develop near the end of week 3 (fig. 315.Moore and Persaud. Most of it passes into the ductus arteriosus into the aorta. By the beginning of week 4. it is a horseshoe-shaped cavity in the cardiogenic and lateral mesoderm. Defects will commonly involve a patent foramen ovale (The Developing Human.Clinically Oriented Embryology . 7th ed. y y Changes that will result in a normal adult circulation occurs during infancy. ductus arteriosus. The fetal circulation is designed to carry oxygenated blood from the placenta to the fetal circulation. 8th ed. 313) and/or patent ductus arteriosus (The Developing Human. p. ductus venosus and umbilical vessels are no longer needed and they close (The Developing Human. A small amount of blood from the right atrium mixes with blood from the superior vena cava and coronary sinus.. updated 9/14/2008 Development of the body cavities and the diaphragm The Developing Human . The curve of the horseshoe represents the future pericardial cavity (fig. and upper limbs receive welloxygenated blood. A small amount passes into the lungs. the rest supplies the viscera and the inferior 1/2 of the body. blood passes into the left ventricle and the ascending aorta. 14-47). After birth. Arteries to the heart. head and neck. 373.

8-12) and is due to failure of fusion between the pleuroperitoneal membranes and other diaphragmatic components. 8-2F). During weeks 5 and 6. 8-11. 4) the body wall. during formation of the diaphragm.8-10. 3) the dorsal mesentery of the esophagus. 8-4C-D). Fusion of the caudal pleuroperitoneal membranes ( fig. 8-6 & fig. the splanchnic layer of the mesoderm encloses the primitive gut and suspends it from the dorsal body wall by a double-layered peritoneal membrane known as the dorsal mesentery. 2) the pleuroperitoneal membranes. 8-8 & 8-9): 1) the septum transversum. the embryonic pericardial cavity communicates with the peritoneal cavity through paired pericadioperitoneal canals (fig.During folding of the embryonic disc in week 4. 8-5). separates the pleural cavities from the peritoneal cavity. As the peritoneal portions of the intraembryonic coelom come together. A posterolateral defect of the diaphragm results in congenital diaphragmatic hernia (figs. partitions form near the cranial and caudal ends of these canals: y y Fusion of the cranial pleuropericardial membranes with mesoderm ventral to the esophagus separates the pericardial cavity from the pleural cavities (fig. The diaphragm forms from (figs. y y When the caudal part of the ventral mesentery disappears. the lateral parts of the intraembryonic coelom are brought together on the ventral aspect of the embryo (fig. 8-7). the right and left parts of the intraembryonic coelom merge and form the peritoneal cavity. Until week 7. updated 09/25/2008 Embryology of the abdominal contents . 8-7.

8th edition Chapter 11 The primitive gut forms during week 4 when the embryo folds and incorporates the dorsal part of the yolk sac (fig. derived from the septum transversum. y y y The endoderm of the primitive gut gives rise to the epithelial lining of most of the digestive tract. 11-1). Between the layers of the ventral mesentery. these primordial cells differentiate into the parenchyma of the liver and the lining of the ducts of the biliary system. respectively. The epithelial liver cords and primordia of the biliary system which develop from the hepatic diverticulum. with or without fistulas between them.The Developing Human . trachea and esophagus have a common origin. The epithelium of the cranial and caudal ends of the digestive tract is derived from the ectoderm of the stomodeum and proctodeum (fig. Development of the duodenum . and the biliary apparatus. biliary passages and parenchyma of liver and pancreas. Because. imcomplete partitioning of the trachoesophageal septum results in stenoses or atresias. Bile formation starts on week 12. grow into the mesenchymal septum transversum (fig. the pancreas. the liver. the duodenum (proximal to the opening of the bile duct). 8-9).Clinically Oriented Embryology . 11-1). The muscular and connective tissue components of the digestive tract are derived from splanchnic mesenchyme surrounding the primitive gut. Development of the liver The liver bud or hepatic diverticulum is formed from an outgrowth of the endodermal epithelial lining of the foregut (fig.Moore and Persaud. y y Hemopoiesis in the liver starts on week 6. the esophagus. the lower respiratory system. The FOREGUT gives rise to: y y y y y y y the pharynx. 11-5).

During week 10. the ascending colon. 11-17). 11-13 A-B). the vermiform appendix. y y While in the umbilical cord. the cecum. the ileum. Malformations: Omphalocele (fig. p. an accessory pancreatic duct forms. Obstruction of the duodenum can also be caused by an annular pancreas (fig. 11-6). the intestines return to the abdomen. 11-13C-D). fig. Because the gut is normally occluded during weeks 5 and 6 due to rapid mitotic activity of its . This process occurs following the normal solid stage of the duodenum (week 5). This is the reduction of the midgut hernia. 11-10) originating from the endodermal lining of the foregut.Congenital duodenal atresia is due to the failure of vacuolization and recanalization (week 8. malrotations and abnormalities of fixation result from failure of return or abnormal rotation of the intestines in the abdomen. The MIDGUT gives rise to: y y y y y y y the duodenum distal to the bile duct. and the right 1/2 to 2/3 of the transverse colon. 285. 11-13. rotating a further 180 degrees (The Developing Human. resulting from parts of the pancreas developing around the duodenum. the midgut loops rotates 90 degrees counterclockwise (fig. The ventral pancreatic bud forms most of the head of the pancreas and the dorsal pancreatic bud forms the rest. The midgut forms a U-shaped intestinal loop herniating into the umbilical cord during week 6 because of the lack of room in the abdomen : This is the physiological umbilical herniation (fig.. 6th ed. When the duodenum rotates to the right. the jejunum. the ventral pancreatic bud moves dorsally and fuses with the dorsal pancreatic bud. fig. Development of the pancreas The pancreas is formed by dorsal and ventral pancreatic buds (fig. 11-14). If the duct systems from each pancreas fail to fuse. 11-11).

Various remnants of the yolk stalk may persist such as Meckel's (ileal) diverticulum (fig. 8th edition Chapter 12 The urogenital system develops from: y the intermediate mesoderm (fig. the sigmoid colon . The Hindgut gives rise to: y y y y y the left 1/3 to 1/2 of the transverse colon. 11-24) may result if the recanalization fails to occur or occur abnormally.Moore and Persaud. The inferior part of the anal canal develops from the proctodeum (fig. Malformations: y y Anorectal malformations result from abnormal partitioning of the cloaca by the urorectal septum into the rectum and anal canal posteriorly and the urinary bladder and urethra anteriorly (fig. atresias and duplications (fig. 11-25) is divided by the urorectal septum into the urogenital sinus and rectum. 11-26). stenosis.epithelium. Arrested growth and/or deviation of the urorectal septum in a dorsal direction causes most of the anorectal abnormalities such as rectal atresia and fistulas between the rectum and urethra. 11-22) which can become inflamed and produce pain. the rectum. The urogenital sinus gives rise to the urinary bladder and urethra. urinary bladder or vagina. . the descending colon. The caudal part of the hindgut (the cloaca. 11-21. The rectum and superior anal canal are separated from the outside by the anal membrane which breaks down by the end of week 8. 12-1B). fig. updated 09/25/2008 Urogenital system embryology The Developing Human . fig.Clinically Oriented Embryology . and the superior part of the anal canal. 11-29).

leaving behind the pronephric ducts which run to the cloaca (fig. its first 4 generations of tubules to the major calyces. 12-2A) and a gonadal or genital ridge (fig.y y the mesodermal epithelium (mesothelium) of the peritoneal cavity. The metanephros develops mesodermally from the metanephric diverticulum or ureteric bud which is a dorsal outgrowth from the mesonephric duct near the cloaca (fig. rudimentary pronephroi develop early in week 4. 12-6C). . and the endoderm of the urogenital sinus (fig. 12-29C). 3 successive sets of kidneys develop: y y y The nonfunctional. It forms the urogenital ridge (fig. The metanephric diverticulum or ureteric bud penetrates the metanephric mesoderm in the caudal part of the nephrogenic cord and stimulates the formation of the metanephric mass or cap (fig. o If esophageal or duodenal atresia occurs. oligohydramnios results. then moved away from the somites during the lateral fold. 12-1F) which is comprised of: y y a nephrogenic cord or ridge (fig. This excretion continues during fetal life and the fetus swallows this urine mixed in the amniotic fluid. But they degenerate. They are functional by week 11-13 and excrete urine into the amniotic fluid. its second 4 generations to the minor calyces (fig. then polyhydramnios results. 12-9). y y y y y Its stalk gives rise to the ureter (fig. These ducts will remain for other kidneys. 12-6E). 12-2). 12-20A). The intermediate mesoderm used to lie lateral to the somites. o If renal agenesis or urethral obstruction occurs. its cranial end to the renal pelvis. It is then absorbed in the stomach and duodenum to the blood for transport to the placenta and disposal. The functional metanephroi or permanent kidneys develop early in week 5. serving as temporary excretory organs. 12-6). 12-6D) and the remaining generations of tubules to the collecting tubules (fig. The mesonephroi develop later during week 4.

the blood supply changes continuously so that an adult may have 2 to 4 renal arteries (fig. They reach the adult position by week 9 having touched the suprarenal glands (fig. and the caudal or phallic region. The kidneys rotate 90 degrees from anterior to medial. The female urethra and almost all of the male urethra have the same origin. 12-12F). The transitional epithelium of the bladder develops from endoderm of the urogenital sinus. proximal convoluted tubule. During their ascension. This is due to the disproportionate growth between the lumbar and sacral regions: the sacral region grows faster than the lumbar region. 12-10). the nephrons continue to develop several months after birth. 12-10): The kidneys are first located in the pelvis ventral to the sacrum but gradually ascend to the abdomen. The urinary bladder develops from the urogenital sinus and the surrounding splanchnic mesenchyme (fig. 12-25) Developmental abnormalities of the kidney and excretory passages are common: y Incomplete division of the metanephric diverticulum or ureteric bud results in double ureter (fig. After birth. The urogenital sinus is comprised of 3 regions: y y y The cranial or vesical region which will form the bladder and which is attached to the allantois. 12-20). the medulla from neural crest cells (receiving preganglionic sympathetic fibers from the celiac plexus). The middle or pelvic region. the allantois degenerates and becomes the urachus forming the median umbilical ligament. 12-12B-D) and supernumerary kidney (fig. Ascension of the kidneys (fig. 12-7). 1224. The cortex of the kidney in the newborn contains mostly undifferentiated mesenchyme. loop of Henle and distal convoluted tubule. . Bowman's capsule. 12-11).The metanephric mesoderm gives rise to the nephrons (glomerulus. 12-27): y y The cortex forms from the mesoderm. The glans penis in the male develops from the ectodermal glandular plate (figs. The suprarenal glands ( fig. fig.

Early genital development is referred to as the indifferent stage of sexual development: the external genitalia do not acquire distinct masculine or feminine characteristics until week 12. The reproductive organs in both sexes develop from primordia that are identical at first. 12-33 and 12-34).medial) and paramesonephric (müllerian . At first both the male and the female have 2 pairs of genital or sex ducts: the mesonephric (wolffian . . 12-29C). an embryo has the potential to develop into either a male or a female.lateral) ducts (figs. the underlying mesenchyme and the primordial germ cells.y y Failure of the kidney to "ascend" from its embryonic position in the pelvis results in an ectopic kidney that is abnormally rotated (fig. Testes and ovaries are derived from the mesodermal epithelium (mesothelium) lining the posterior abdominal wall. 12-30). 12-31). Genetic sex is established at fertilization. 1229). The indifferent gonads consist of a cortex and medulla. at the gonadal ridge (fig. In the male (XY) the cortex regresses and the medulla develops (fig. updated 10/06/2008 THE GENITAL OR REPRODUCTIVE SYSTEM develops in close association with the urinary or excretory system. The primordial germ cells form in the wall of the yolk sac during week 4 (fig. They later migrate into the developing gonads at week 6 and differentiate into the definitive germ cells (oogonia/spermatogonia). Various congenital cystic conditions of the kidneys may result from failure of nephrons derived from the metanephric mesoderm to connect with collecting tubules derived from the metanephric diverticulum. y y y y Gonads develop at week 5 from thickened mesodermal epithelium on the medial side of the mesonephros. During this indifferent stage. 12-12B). but the gonads do not begin to attain sexual characteristics until week 7. Primary epithelial sex cords grow into the underlying mesenchyme (fig. The reverse occurs in the female (XX).

uterine tubes are absent.The external genitalia are female but the vagina ends in a blind pouch. y y y In the presence of a Y chromosome. . y y y Male pseudohermaphroditism results from failure of the fetal testes to produce adequate amounts of masculinizing hormones.Gonadal sex is determined by the Y chromosome. Subjects are chromosomally female. The superior end of these ducts open into the future peritoneal cavity. Errors in sexual differentiation cause pseudohermaphroditism. the paramesonephric ducts develop (fig. In the absence of a Y chromosome and in the presence of 2 X chromosomes. also produced by the testes. ovaries develop. The patient is a normal-appearing female with presence of undescended testes and 46. Subjects are chromosomally male. vas deferens and ejaculatory ducts. 12-33B-C). fig. Persons with true hermaphroditism (ovo-testes . a disorder of the fetal suprarenal or adrenal glands that causes excessive production of androgens and masculinization of the external genitalia. Female pseudohermaphroditism results from virilizing adrenal hyperplasia. XY chromosome constitution. A suppressor substance (müllerian inhibiting substance). testes develop and produce an inducer substance stimulating development of the mesonephric ducts into the male genital ducts (epididymis. Androgens from the fetal testes stimulate development of the indifferent external genitalia into the penis and scrotum. which exerts a positive testisdetermining action (TDF) on the indifferent gonad. 12-37D-H). The uterus and uterine tubes are absent. The lower end becomes the uterus and uterine tubes The vagina develops from the vaginal plate derived from the urogenital sinus. and the indifferent external genitalia develop into the clitoris and labia (fig. 12-33A). Androgen insensitivity syndrome: o Previously called testicular feminization syndrome. inhibits development of the paramesonephric ducts.very rare) have both ovarian and testicular tissue and variable internal and external genitalia. or from production of the hormones after the tissue sensitivity of the sexual structures has passed. the mesonephric ducts regress.

12-49A-B) and hydrocele (peritoneal fluid in the processus vaginalis and spermatic cord. 9-4): y y y y Branchial or pharyngeal arches Pharyngeal pouches Branchial grooves Branchial membranes Most congenital malformations of the head and neck originate during transformation of the branchial apparatus into its adult derivatives. 8th edition Chapter 9 The branchial apparatus consists of (figs. fig. updated 10/06/2008 EMBRYOLOGY OF THE BRANCHIAL ARCHES AND DERIVATIVES The Developing Human . Failure of the urogenital folds to fuse normally in males results in various types of hypospadias (opening of the external urethral orifice on the ventral surface of the glans penis or on the ventral surface of the body of the penis. 12-47). This membrane ruptures at about day 24 (fig. Cryptorchidism (undescended testes. 9-3. fig. Congenital inguinal hernia (fig.Moore and Persaud.Clinically Oriented Embryology . fig. . 9-1E). 12-42) or epispadia. fig. 12-48) and ectopic testes result from abnormalities of testicular descent (The gubernaculum guides the processus vaginalis into the scrotum and the testes follow. The primitive mouth or stomodeum is separated from the primitive pharynx by the buccopharyngeal (oropharyngeal) membrane (fig. 12-44). 9-1F). 12-49C-D) result from persistence of the processus vaginalis (communication between the tunica vaginalis and the peritoneal cavity). bringing the primitive gut into contact with the amniotic fluid cavity.Malformations: y y y y Most abnormalities of the female genital tract result from incomplete fusion of the paramesonephric ducts ( fig.

Initially. By the end of week 4. . each pharyngeal arch consists of mesenchyme derived from the intraembryonic mesoderm and is covered with ectoderm externally and endoderm internally. the 5th and 6th being small. creating the swellings of the arches and contributing to the arches. The mesenchyme in the arches give rise to muscles. Neural crest cells give rise to specific skeletal structures. even though they are of ectodermal origin. 9-3C): y y y y an aortic arch a cartilaginous rod a nerve a muscular component Derivatives of the branchial arch cartilages (fig. Branchial arches are separated by the branchial grooves and are numbered in a craniocaudal sequence (fig.Branchial arches develop early in week 4 as neural crest cells migrate to the future head and neck region. A typical branchial arch contains (fig. 4 pairs of branchial arches are visible. 9-3). Neural crest cells migrate into the arches. 9-5B) 1st branchial (mandibular) arch cartilage develops : y y y into malleus and incus (middle ear bones) from its dorsal portion into the anterior ligament of the malleus and the sphenomandibular ligament from the perichondrium of its intermediate portion into the primordium of the mandible from its ventral portion 2nd branchial (hyoid) arch cartilage develops: y y y into the stapes (middle ear) and the styloid process from its dorsal part into the stylohyoid ligament from the perichondrium of its intermediate part into the lesser cornu and the superior part of the hyoid bone from its ventral part 3rd branchial arch cartilage develops into the greater cornu and inferior part of the body of the hyoid bone.

except for the epiglottis which forms from the mesenchyme in the hypobranchial eminence (from the 3rd and 4th branchial arches). Derivative of the branchial arch nerves (fig.4th and 6th branchial arch cartilages fuse to form the laryngeal cartilages. 9-7): y y y y 1st branchial arch: Trigeminal (V) nerve (maxillary and mandibular divisions only) 2nd branchial arch: Facial (VII) nerve 3rd branchial arch: Glossopharyngeal (IX) nerve 4th and 6th branchial arches: Vagus (X) nerve Derivatives of the branchial arch muscles (fig. 9-6): 1st branchial arch: y y y y Muscles of mastication Mylohyoid and anterior belly of the digastric Tensor tympani Tensor veli palatini 2nd branchial arch y y y y Muscles of facial expression Stapedius Stylohoid Posterior belly of the digastric 3rd branchial arch y Stylopharyngeus 4th and 6th branchial arches: y y y y y Cricothyroid Levator veli palatini Constrictors of the pharynx Intrinsic muscles of the larynx Striated muscles of the esophagus .

9-8) and the thymus (elongate portion). 9-9) 1st pharyngeal pouch expands into a tubotympanic recess (fig. 9-8) and the epithelial lining of the fauces.bulbar portion. which migrate inferiorly (past the superior parathyroid glands of the 4th pouch). 3rd pharyngeal pouch contributes to the formation of the inferior parathyroid glands (week 5. updated 11-03-2008 Back to The Lecture Notes page . Only the 1st branchial groove persists in the adult as the external acoustic meatus (fig.PHARYNGEAL POUCHES (fig. the 5th is absent or very small. 4th pharyngeal pouch contributes to the formation of the superior parathyroid gland (bulbar portion) and the parafollicular cells or calcitonin cells of the thyroid gland (elongate portion . 9-8B). Connection between the tubotympanic recess and the pharynx elongates to form the auditory tube.ultimobranchial body). The endoderm of the pharyngeal pouches and the ectoderm of the branchial grooves contact each other to form the branchial membranes separating the pharyngeal pouches and the branchial grooves. y y y The expanded distal portion of the recess contacts the 1st branchial groove (this is the only branchial membrane to persist in the adult) contributing to the formation of the tympanic membrane or eardrum. 2nd pharyngeal pouch contributes to the formation of the palatine tonsil (fig. 9-8) develop between the branchial arches (1st pouch is found between the first and second branchial arches). Derivatives of the pharyngeal pouches (fig. The tubotympanic recess gives rise to the tympanic cavity and the mastoid antrum. There are 4 pairs. fig. 9-8).