Trilaminar Germ Disc.pdf

Trilaminar Germ Disc
(Third Week of Development)

DR. A.U. AGU MBBS, MSc, PhD 1  Outline Gastrulation Formation of the Notochord Establishment of the Body Axes/molecular regulation Fate Map Established During Gastrulat...

Trilaminar Germ Disc
(Third Week of Development)

DR. A.U. AGU MBBS, MSc, PhD 1  Outline Gastrulation Formation of the Notochord Establishment of the Body Axes/molecular regulation Fate Map Established During Gastrulation Growth of embryonic disc Clinical correlates 2  Gastrulation Is the process of establishment of the 3 germ layers (ectoderm, mesoderm, & endoderm) in the embryo It is the most characteristic event occurring during the 3rd wk of gestation Begins with formation of the primitive streak on the surface of the epiblast. Initially, the streak is ill defined 3  In a 15 – 16 day embryo, the streak is seen as a narrow groove with slightly bulging regions on either side. The cephalic end of the streak (primitive node) consists of a slightly elevated area surrounding the primitive pit. 4  Cells of the epiblast migrate toward the primitive streak, become flask-shaped, detach from the epiblast, & slip beneath it. Some displace the hypoblast, creating the embryonic endoderm, & others come to lie b/w the epiblast & newly formed endoderm to form mesoderm. Cells remaining in the epiblast then form ectoderm. Thus, the epiblast, through the process of gastrulation, forms the 3 germ layers & 5  As more & more cells move b/w the epiblast & hypoblast layers, they begin to spread laterally & cephalad. Gradually, they migrate beyond the margin of the disc & establish contact with the extraembryonic mesoderm covering the yolk sac & amnion. In the cephalic direction, they pass on each side of the prechordal plate. 6  The prechordal plate is b/w the tip of the notochord & the buccopharyngeal membrane & is derived from some of the 1st cells that migrate through the node in a cephalic direction. the prechordal plate will be important for induction of the forebrain The buccopharyngeal membrane represents the future opening of the oral cavity. 7 Formation of the Notochord The cranial end of primitive streak becomes thickened & is called primitive node A depression (pit) appears in the center of the node Cells in the node multiply & pass cranially in the midline b/w the ectoderm & 8  The cavity of the pit extends into the process & converts it into tube called notochordal canal The walls of the canal flattened to form the notochordal plate The process of flattening soon get reversed & the plate assumes a tube which is converted into a solid rod of cells called definitive notochord 9  Establishment of the Body Axes (anteroposterior, dorsoventral, & left-right) Takes place before & during the period of gastrulation. The anteroposterior axis is signaled by cells at the anterior (cranial) margin of the embryonic disc (anterior visceral endoderm (AVE)). This area expresses genes essential for head formation, (ie the transcription factors OTX2, LIM1, HESX1 & the secreted factor cerberus). – They establish the cranial end of the embryo before gastrulation. 10  The primitive streak is initiated & maintained by expression of Nodal, (member of the transforming growth factor β (TGF-β) family). Once the streak is formed, a number of genes regulate formation of dorsal & ventral mesoderm, head & tail structures. 11  Another member of the TGF-β family, (BMP-4) is secreted throughout the embryonic disc. In the presence of BMP-4 & fibroblast growth factor (FGF), mesoderm will be ventralized to contribute to kidneys (intermediate mesoderm), blood, & body wall mesoderm (lateral plate mesoderm). In fact, all mesoderm would be ventralized if the activity of BMP-4 were not blocked by other genes expressed in the node. 12  Hans Spemann termed the node ‘organizer’. Chordin (activated by the transcription factor Goosecoid ), noggin, & follistatin antagonize the activity of BMP-4. Thus, cranial mesoderm is dorsalized into notochord, somites, & somitomeres. Later, these 3 genes are expressed in the notochord & are important in neural induction in the cranial region. 13  HNF-3β maintains the node & later induces regional specificity in the forebrain & midbrain areas. Without HNF-3β, embryos fail to gastrulate properly & lack forebrain & midbrain structures. Goosecoid activates inhibitors of BMP-4 & contributes to regulation of head development. Thus, Overexpression or underexpression of this gene results in severe malformations of the head region. 14  Regulation of dorsal mesoderm formation in mid & caudal regions of the embryo is controlled by the Brachyury (T) gene Its absence results in shortening of the embryonic axis (caudal dysgenesis). The degree of shortening depends upon the time at which the protein becomes deficient. 15  Left-right sidedness is also orchestrated by a cascade of genes. Fibroblast growth factor 8 (FGF-8) is secreted by cells in the node & primitive streak & induces expression of Nodal on only the left side of the embryo. FGF-8 maintains Nodal expression in the lateral plate mesoderm as well as Lefty-2, & both of these genes upregulate PITX2, a transcription factor responsible for establishing left sidedness Simultaneously, Lefty-1 is expressed on the left side of the floor plate of the neural tube & may act as a barrier to prevent left-sided 16  Sonic hedgehog (SHH) serves as a repressor for left sided gene expression on the right. The Brachyury(T) gene, secreted by the notochord, is also essential for expression of Nodal, Lefty-1, & Lefty-2. Genes regulating right-sided development are not as well defined. Although, expression of the transcription factor NKX 3.2 is restricted to the right lateral plate mesoderm & probably regulates effector genes responsible for establishing the right side. 17  Fate Map Established During Gastrulation Regions of the epiblast that migrate & ingress through the primitive streak have been mapped & their ultimate fates determined. For example; – Cells that ingress through the cranial region of the node become notochord – Those migrating at the lateral edges of the node & 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 – Cells migrating through the caudal-most part of the streak contribute to extraembryonic mesoderm 18  Growth of the Embryonic Disc Initially, the embryonic disc was flat & almost round. Gradually, it becomes elongated with a broad cephalic & a narrow caudal end. The expansion occurs mainly in the cephalic region & the region of the primitive streak remains more or less the same size. Growth & elongation of the cephalic part are caused by a continuous migration 19 of cells from the primitive  The migration of the cells forward & laterally continues until the end of the 4th wk. The supply of new cells by the primitive streak until the end of the 4th wk is important on development of the embryo. – In the cephalic part, germ layers begin their specific differentiation by the middle of the 3rd wk whereas in the caudal part, differentiation begins by the end of the 4th wk. – Thus gastrulation, continues in caudal segments while cranial structures are 20  CLINICAL CORRELATES Teratogenesis Associated With Gastrulation Holoprosencephaly - a deficiency of the midline in craniofacial structures due to high doses of alcohol that kill cells in the anterior midline of the germ disc. Features are; – Small forebrain, – The 2 lateral ventricles often merge into a single ventricle – The eyes are close together (hypotelorism). 21  Caudal dysgenesis (sirenomelia), Insufficient mesoderm is formed in the caudal-most region of the embryo, B/c the mesoderm contributes to formation of the lower limbs, urogenital system, & lumbosacral vertebrae. Affected individuals exhibit a variable range of defects, Sirenomelia (caudal including dysgenesis). Loss of – Hypoplasia & fusion of the lower mesoderm in the lumbosacral region limbs, – Vertebral abnormalities, – Renal agenesis, – Imperforate anus, 22 – Anomalies of the genital organs. Situs inversus Transposition of the viscera in the thorax & abdomen About 20% of patients with complete situs inversus also have bronchiectasis & chronic sinusitis b/c of abnormal cilia (Kartagener syndrome). Other conditions of abnormal sidedness are known as laterality sequences. Patients with these conditions do not have complete situs inversus but appear to be predominantly bilaterally left sided or right sided. 23 Sacrococcygeal teratoma Results from remnants of the primitive streak. These tumors may become malignant & are most common in females contain tissues derived from all 3 germ layers 24  THANKS FOR LISTENING 25