Third Week of Development: Trilaminar Germ Disc

Third Week of Development: Trilaminar Germ Disc GASTRULATION: The process that establishes all three germ layers(ectoderm , mesoderm , and endoderm) in the embryo. Gastrulation begins with formation of the primitive streak on the surface of the epiblast In a 15- to 16-day embryo, it is clearly visible as a narrow groove with slightly bulging regions on either side. Primitive node , The cephalic end of the streak, consists of a slightly elevated area surrounding the small primitive pit Cells of the epiblast migrate toward the primitive streak Invagination : Upon arrival in the region of the streak, they become flask-shaped, detach from the epiblast, and slip beneath it fibroblast growth factor 8 (FGF8) (is synthesized by streak cells themselves): Cell migration and specification cell movement by downregulating E-cadherin(normally binds epiblast together) cell specification into the mesoderm by regulating BRACHYURY (T) expression Once the cells have invaginated, some displace the hypoblast, creating the embryonic endoderm , and others come to lie between the epiblast and newly created endoderm to form mesoderm. Cells remaining in the epiblast then form ectoderm . Thus, the epiblast, through the process of gastrulation, is the source of all of the germ layers • As more and more cells move between the epiblast and hypoblast layers, they begin to spread laterally and cranially . • Gradually, they migrate beyond the margin of the disc and establish contact with the extraembryonic mesoderm covering the yolk sac and amnion. • In the cephalic direction, they pass on each side of the prechordal plate . • The prechordal plate itself forms between the tip of the notochord and the oropharyngeal membrane and is derived from some of the first cells that migrate through the node in the midline and move in a cephalic direction. • The oropharyngeal membrane at the cranial end of the disc consists of a small region of tightly adherent ectoderm and endoderm cells that rerepresents the future opening of the oral cavity. Formation of the notochord : Prenotochordal cells invaginating in the primitive node move forward cranially in the midline until they reach the prechordal plate (A) These prenotochordal cells become intercalated in the hypoblast so that for a short time, the midline of the embryo consists of two cell layers that form the notochordal plate (B ). As the hypoblast is replaced by endoderm cells moving in at the streak, cells of the notochordal plate proliferate and detach from the endoderm. They, then form a solid cord of cells, the definitive notochord.(C) With further development, the plate detaches from the endoderm, and a solid cord, the notochord , is formed. It forms a midline axis, which will serve as the basis of the axial skeleton(a signalling center for inducing the axial skeleton.) The notochord and prenotochordal cells extend cranially to the prechordal plate (an area just caudal to the oropharyngeal membrane) and caudally to the Primitive pit. At the point where the pit forms an indentation in the epiblast, the neurenteric canal temporarily connects the amniotic and yolk sac cavities Cloacal membrane:(at the caudal end of the embryonic disc ) This membrane, which is similar in structure to the oropharyngeal membrane, consists of tightly adherent ectoderm and endoderm cells with no intervening mesoderm. Allantois(allantoenteric diverticulum ): When the cloacal membrane appears, the posterior wall of the yolk sac forms a small diverticulum that extends into the connecting stalk.(around the 16th day) Initially cells move along surface (blue arrows) but upon reaching the center line (primitive streak) will enter the embryo, turn the corner and move internally (red arrows). The Three Germ Layers Ectoderm Mesoderm Notochord Endoderm (Part of the mesoderm) • Ectoderm: skin, CNS, PNS, eyes, internal ear, neural crest cells (bones and connective tissue of the face and part of the skull) • Mesoderm: bones, connective tissue, urogenital system, cardiovascular system • Endoderm: gut and gut derivatives (liver, pancreas, lungs, etc.) Mammalian Pattern & Polarity Humans, like most other living things, have a distinct organization. Thus the head is at one end while the feet are at the opposite end (AnteriorPosterior Axis; A-P axis or Craniocaudal). The face is one side (ventral) with the limbs and other body parts organized to function in this direction as opposed to backwards (dorsal) thus defining the dorsal-ventral axis. We also have right and left sides (Right-Left Axis). These three axes become established during early development ESTABLISHMENT OF THE BODY AXES Establishment of the body axes , occurs early in Embryogenesis. By the blastocyst stage, the A–P axis is determined and cells that are destined to form the anterior visceral endoderm (AVE) at the cranial end of the endoderm layer of the bilaminar disc migrate toward what will become the head region. Inhibit nodal activity:OTX2,LIM1,HESX1 Cerebrus & Lefty At this bilaminar disc stage, cells in the AVE express genes essential for head formation, including the transcription factors OTX2, LIM1,and HESX1,and the secreted factors Cerberus and lefty1 (members of the TGF- β family), which inhibit nodal activity, thereby establishing the cranial end of the embryo. The absence of cerberus and lefty1 at the caudal end of the embryo allows nodal expression to continue, and maintains the primitive streak. Bone morphogenetic protein 4 (BMP4) , (TGF-β) is secreted throughout the embryonic disc : In the presence of this protein and FGF , mesoderm will be ventralized to (intermediate mesoderm), and (lateral plate mesoderm). The node is the organizer .The activity of BMP4 were blocked by other genes expressed in the node. CHORDIN (activated by the transcription factor GOOSECOID ), noggin , and follistatin antagonize the activity of BMP4. As a result, cranial mesoderm is dorsalized into notochord, somites, and somitomeres Nodal is involved in initiating and maintaining the primitive streak Similarly, HNF-3 β maintains the node and later induces regional specificity in the forebrain and midbrain areas. Over- or underexpression of GOOSECOID in laboratory animals results in severe malformations of the head region, including duplications, similar to some types of conjoined twins BRACHYURY (T) gene expressed in the node, notochord precursor cells, and notochord. This gene is essential for cell migration through the primitive streak. Mesoderm formation in these regions depends on this gene product, and its absence results in shortening of the embryonic axis (caudal dysgenesis). Caudal dysgenesia Laterality (L–R sidedness) also is established early in development. When the primitive streak appears, FGF8 is secreted by cells in the node and primitive streak, and this growth factor induces expression of NODAL. NODAL expression is then restricted to the left side of the embryo by the accumulation of serotonin (5-HT) on the left side. Midline genes like SONIC HEDGEHOG ( SHH ), LEFTY1 , and ZIC3 are involved in establishing the midline but also prevent NODAL expression from crossing over to the right side(midline barriers) Nodal protein in the left lateral plate mesoderm initiates a signaling cascade that includes LEFTY2 to upregulate PITX2 PITX2 is a homeobox-containing transcription factor that is a “master gene” responsible for establishing left -sidedness, and its expression is repeated on the left side of the heart, stomach, and gut primordia. The neurotransmitter 5-HT(5hydroxytryptamine)(Serotonin) also plays a critical role in this signaling cascade. 5-HT is concentrated on the left side, and restricts Nodal signaling to the left side. The transcription factor SNAIL is restricted to the right lateral plate mesoderm and probably regulates effector genes responsible for establishing the right side. FATE MAP ESTABLISHED DURING GASTRULATION Cells that ingress through the cranial region of the node become prechordal plate and notochord; Those migrating at the lateral edges of the node and from the cranial end of the streak become paraxial mesoderm ; Cells migrating through the midstreak region become intermediate mesoderm ; Those migrating through the more caudal part of the streak form lateral plate mesoderm ; and Cells migrating through the caudal most part of the streak contribute to extraembryonic mesoderm The embryonic disc, initially flat and almost round, gradually becomes elongated, with a broad cephalic and a narrow caudal end Growth and elongation of the cephalic part of the disc are caused by a continuous migration of cells from the primitive streak region in a cephalic direction. In the cephalic part, germ layers begin their specific differentiation by the middle of the third week, whereas in the caudal part, differentiation begins by the end of the fourth week. Thus, gastrulation, or formation of the germ layers, continues in caudal segments while cranial structures are differentiating, causing the embryo to develop cephalocaudally. FURTHER DEVELOPMENT OF THE TROPHOBLAST By the beginning of the 3rd week: primary villi that consist of a cytotrophoblastic core covered by a syncytial layer Secondary villus: During further development, mesodermal cells penetrate the core of primary villi and grow toward the decidua. Tertiary villus or a definitive placental villus :By the end of the third week, mesodermal cells in the core of the villus begin to differentiate into blood cells and small blood vessels, forming the villous capillary system A 13-day-old implantation site showing primary villi Presomite embryo and the trophoblast at the end of the third week. Tertiary and secondary stem villi give the trophoblast a characteristic radial appearance. Capillaries in tertiary villi make contact with capillaries developing in the mesoderm of the chorionic plate and in the connecting stalk These vessels, in turn, establish contact with the intraembryonic circulatory system, connecting the placenta and the embryo. Hence, when the heart begins to beat in the fourth week of development, the villous system is ready to supply the embryo proper with essential nutrients and oxygen. Meanwhile, cytotrophoblastic cells in the villi penetrate progressively into the overlying syncytium until they reach the maternal endometrium. Here they establish contact with similar extensions of neighboring villous stems, forming a thin outer cytotrophoblast shell Outer cytotrophoblast shell:This shell gradually surrounds the trophoblast entirely and attaches the chorionic sac firmly to the maternal endometrial tissue Stem or anchoring villi : Villi that extend from the chorionic plate to the decidua basalis ( decidual plate) Those that branch from the sides of stem villi free (terminal) villi ,through which exchange of nutrients and other factors will occur. The chorionic cavity, meanwhile, becomes larger, and by the 19th or the 20th day, the embryo is attached to its trophoblastic shell by a narrow connecting stalk . The connecting stalk later develops into the umbilical cord, which forms the connection between the placenta and embryo.