Development: Trilaminar Germ Disc

By Dr. AAIJAZ AHMED KHANSR.LECTURER JABATAN ANATOMY

Gastrulation- The process of formation of germ layers ( endoderm, mesoderm and ectoderm) in the embryoIt occurs during the third week of gestationGastrulation begins with the formation of the primitive streak on the surface of epibalstIn a 15-16 day embryo primitive streak visible as narrow groove with slightly bulging regions on either side.The cephalic end of the streak, the primitive node a slightly elevated area surrounding the small primitive pit

A - Dorsal view of a 16 days embryo ( primitive node and streak visible)B- Dorsal view of a 18 days embryo

Cells of the epiblast migrate toward the primitive streakReaching near the primitive streak these cells become flask shaped, detach from the epiblast, and slip beneath it. (invagination) - Some of these cells displace the hypoblast, forming embryonic endoderm -Cells which come to lie between the epiblast and newly formed endoderm form mesoderm.-Cells remaining in the epiblast form ectoderm ( The epiblast is the source of all of the germ layers)

Formation of NotochordPrenotochordal cells invaginating in the primitive pit move forward cephalad to reach the prechordal plateThese prenotochordal cells become intercalated in the hypoblast at this stage embryo consists of two cell layers that form the notochordal plateCells of the notochordal plate proliferate and detach from the endoderm to form a solid cord of cells, the definitive notochord. It serves as the basis of the axial skeleton.The notochord and prenotochordal cells extend cranialy to the prechordal plate (an area just caudal to the buccopharyngeal membrane) and caudally to the primitive pit.

At the point where the pit forms an indentation in the epiblast, the neurantic canal temporarily connects the amniotic and yolk sac cavities

The cloacal membrane is formed at the caudal end of the embryonic disc. It consists of tightly adherent ectoderm and endodermAt the same time the posterior wall of the yolk sac forms a small diverticulum that extends into the connecting stalk. This diverticulum is called the allantoentric diverticulum or allantois. This appears at about 16th day of development.

Establishment of the body axesEstablishment of the body axes-anteroposterior,dorsoventral and left right, takes place prior to and during the period of gastrulation The anteroposterior axis is signaled by cells of the posterior margin of the embryonic disc. This Posterior marginal zone (PMZ) secretes an activin like molecule that induces primitive streak formation. This establishes the cranio to caudal axis in the embryo.

Fate Map established during GastrulationRegions of the epiblast that migrate and ingress through the primitive streak have been maped and their ultimate fates determined.Cells that ingress through the cranial region of the node become notochordThose migrating at the lateral edges of the node and from the cranial end of the streak become paraxial mesodermCells migrating through the mid streak region become intermediate mesodermThose migrating through the caudal part of the streak form lateral plate mesoderm

TS showing formation of mesoderm A- 17 day B 19 day

Growth of the Embryonic DiscThe embryonic disc, initially flat and almost round, gradually becomes elongated, with broad cephalic and a narrow caudal endExpansion of the embryonic disc occurs mainly in the cephalic region; the region of the primitive streak remains more or less the same size Growth and elongation of the cephalic part of the disc are caused by a continuous migration of cells from the primitive streak in the cephalic direction. This continues until the end of the fourth weekAt the end of the fourth week the primitive streak shows regressive changes, rapidly shrinks and disappearsIn the cephalic part , germ layers begin their specific differentiation by the middle of the third week In the caudal part, differentiation begins by the end of the fourth week

Derivatives of the germ layersThe embryonic period or period of organogenesis ( 3rd to 8th week of development)- During this period the three germ layers, ectoderm, mesoderm and endoderm, gives rise to a number of specific tissue and organs.

EctodermAt the third week of development the ectoderm is disc shaped, broader in the cephalic than the caudal regionAppearance of the notochord and prechordal mesoderm induces the overlying ectoderm to thicken and form the neural plate. Cells of the plate make up neuroectoderm, initial event in the process of neurilation.

NeurilationThe process, can be divided into four stages:(1) Local elongation of the ectoderm cells in a midline zone of the disc and their reorganization into a pseudostratified epithelium, the neural plate.(2)Reshaping of the neural plate.(3)Bending of the plate into a neural groove.(4)Closure of the neural groove into a neural tube from the midportion to its cranial and caudal ends

After induction, the elongated, slipper-shaped neural plate gradually expands toward the primitive streakBy the end of the 3rd week, the lateral edges of the neural plate become more elevated to form neural folds,and the depressed middle portion forms the neural grooveGradually the neural folds approach each other in the midline and fuse to form neural tube. This fusion begins in the region of the future neck (5th somite) Until fusion is complete, the cephalic and caudal ends of the neural tube communicte with the amniotic cavity by cranial and caudal neuropores Closure of the cranial neuropore occurs approximately at day 25( 18-20 somite stage)Posterior neuropore closes at day 27 ( 25 somite stage)

Formation of neural groove and fold

Neurilation is then complete,and the central nervous system is represented by a closed tubular structure with a narrow caudal portion, the spinal cord and broader cephalic portion, the brain vesicle By the time neural tube is closed, two bilateral ectodermal thickenings the otic placodes and the lens placodes, become visible in the cephalic region.Otic placodes invaginate and form the otic vesicles, which will develop into structures needed for hearing and equilibriumLens placodes invaginate and form the lenses of the eyes ( During 5th week)

Neural crestAs the neural folds elevate and fuse, cells at the lateral border or crest of the neuroectoderm begin to dissociate, this cells population, the neural crest will under go an epithelial-to-mesenchymal transition as it leaves the neuroectoderm by active migration and displacement to enter the underlying mesoderm.Derivatives of the neural crest- crest cells give rise to a heterogeneous array of tissues

Formation and migration of neural crest cells in the spinal cord

Derivatives of the neural crest-Connective tissue and bone of the face and skullCranial nerve gangliaAdrenal medullaDermis in the face and neckArachnoid and piamater (leptomeninges)Spinal (dorsal) root gangliaSympathetic chain and preaortic gangliaParasympathetic ganglia of the GITCells Melanocytes - Glial cells - Schwann cells - Odontoblasts - C cells of the thyroid

SummaryThe ectoderm gives rise to organs and structures that maintain contact with the outside worldE.G.The central nervous systemThe peripheral nervous systemThe sensory epithelium of the ear, nose and eyesThe epidermis including the hair and nailsSubcutaneous glands, the mammary glands, the pituitary gland and enamel of the teeth

Mesodermal Germ layer DerivativesBy about 17th day mesodermal cells close to the midline proliferate and form a thickened plate called paraxial mesoderm More laterally the mesoderm layer remains thin and called as lateral plate mesodermIntermediate mesoderm connects paraxial and lateral plate With the appearance and coalescence of intercellular cavities in the lateral plate it divides into two layers1. Somatic or parietal mesoderm layer- a layer continuous with mesoderm covering the amnion 2. Splanchnic or visceral layer- a layer continuous with mesoderm covering the yolk sac (Together these layers line a newly formed cavity, the intraembryonic cavity. )

Paraxial MesodermBy the beginning of third week, paraxial mesoderm is organised into segemnts somitomeres Somitomeres first appear in the cephalic region and then proceeds cephalocaudally Each somitomeres is consists of mesodermal cells arranged in concentric whorlIn the head region somitomeres form in association with segmentation of neural tube into neuromeres. ( Which contribute the majority of the head mesenchyme)From the occipital region caudally, somitomeres organize into Somites.The first pair of somites arises in the cervical region of the embryo at the 20th day of development

Formation of somites

Approximately 3 pairs of somites appear per dayAt the end of the 5th week, 42 to 44 pairs are presentThere are 4 occipital, 8 cervical, 12 thoracic, 5 lumber, 5 sacral and 8-10 coccygeal pairsThe first occipital and the last 5-7 coccygeal somites later disappear. The remaining form the axial skeleton.During this period the age of the embryo is expressed in number of somites

Number of somites correlated to Approximate age in days

- Sclerotome- Cells forming the ventral and medial walls of the somite become polymorphous and shift to surround the notochord. These cells collectively known as scleretome.They will surround the spinal cord and notochord to form the vertebral columnCells at the dorsolateral portion of the somite migrate as precursors of the limb and body wall musculature.Cells at the dorsomedial portion of the somite proliferate and migrate down the ventral side of the somite to form Myotome.The remaining dorsal epithelium forms the Dermatome and together these layers constitute the dermotomyotome

Each segmentally arranged myotome contributes to the muscles of the back ( epaxial musculature)The dermatomes disperse to form the dermis and subcutaneous tissue of the skinEach myotome and dermatome retains its innervation from its segment of origin*Hence each somite forms its own sclerotome(the cartilage and bone), myotome (muscle) and dermatome ( the segmental skin component).* Each myotome and dermatome has its own segmental nerve component.

Intermediate MesodermWhich temporarily connects paraxial mesoderm with lateral plate mesodermIt differentiates into urogenital structuresLateral plate Mesoderm -It splits into parietal and visceral layers, which respectively line the intraembryonic cavity and surround the organs - Parietal mesoderm, together with overlying ectoderm,will form lateral and ventral body wall - Visceral mesoderm and embryonic endoderm will form the wall of the gut - Mesodermal cells of the parietal will form mesothelial membranes, or serous membranes (lining of the pleural, peritoneal and pericardial cavities)

SummaryFollowing tissues and organs are developed from the mesoderm:-- Supporting tissues- connective tissue, cartilage and bone-striated and smooth musculatures- The walls of the heart,blood and lymph vessels-Blood and lymph cells-Kidney, Gonads and their corresponding ducts- The cortex of the suprarenal gland-The spleen

Derivatives of the EndodermThe gastrointestinal tract is the main organ system develop from the endoderm.The endoderm covers the ventral surface of the embryo and forms the roof of the yolk sac With the development and growth of the brain vesicles, the embryonic disc begins to bulge into the amniotic cavity and to fold cephalo-caudally. The head and tail folds are formed because of folding.As a result of cephalocaudal folding, a large portion of the endoderm lined cavity is incorporated into the body of the embryo properIn the anterior part it forms foregut; in the tail region it forms the hind gut. The part between fore and hind gut is the midgut

The midgut temporarily communicates with the yolk sac by Vitelline duct. This duct is wide initially,but later on it becomes narrow and longerA- presomite embry B- 7 somites embryo

At its cephalic end, the foregut is bounded by the buccopharyngeal membrane ( an ectodermal-endodermal membraneIn the 4th week the buccopharyngeal membrane ruptures, establishing an open connection between the amniotic cavity and the primitive gutThe cloacal membrane temporarily separates the hind gut from the amniotic cavity.The cloacal membrane breaks down in the 7th week to create the opening for the anusAs a result of cephalocaudal and lateral folding, allantois is partially incorporated into the body of embryo, where it forms cloaca. The distal portion of the allantois remains in the connecting stalk

By the 5th week, the yolk sac duct, allantois and umbilical vessels are restricted to the umbilical ring. In humans the yolk sac is a vestigial and probably has nutritive role in the early stages

Summary:- following tissues and organs are developed from the endodermThe epithelial lining of the respiratory tractThe epithelial lining of the Gastrointestinal tractThe parenchyma of the thyroid, parathyroids, liver & pancreasThe reticular stroma of the tonsils and thymus The epithelial lining of the urinary bladder and urethraThe epithelial lining of the tympanic cavity and auditory tube