Chapter 5: Third Week of Development: Trilaminar Germ Disc

Third Week of Development: Trilaminar Germ Disc from Langman’s Medical Embryology details the critical third week of human development, characterized primarily by gastrulation, the process that converts the bilaminar disc into a trilaminar germ disc consisting of ectoderm, mesoderm, and endoderm. The narrative begins with the formation of the primitive streak and primitive node on the surface of the epiblast, controlled by Fibroblast Growth Factor 8 (FGF8), which downregulates E-cadherin to facilitate cell migration and invagination. As epiblast cells displace the hypoblast, they establish the definitive endoderm and intraembryonic mesoderm, with the remaining epiblast cells becoming the ectoderm. The chapter thoroughly explains the formation of the notochord, a key signaling center for the axial skeleton, describing how prenotochordal cells move cranially to the prechordal plate and temporarily form the neurenteric canal. Significant attention is given to the molecular establishment of body axes (anterior-posterior, dorsal-ventral, and left-right), highlighting the role of the Anterior Visceral Endoderm (AVE) in head formation via transcription factors like OTX2 and LIM1, and the "organizer" function of the node in dorsalizing mesoderm through factors like Chordin and Noggin which antagonize BMP4. The text further elucidates the establishment of laterality, where a cascade involving Serotonin (5-HT), Nodal, and the master gene PITX2 dictates left-sided organ positioning, noting that ciliary dysfunction can lead to situs inversus or heterotaxy. Additionally, the chapter outlines the fate map of the epiblast, correlating migration through specific streak regions with the formation of the paraxial, intermediate, and lateral plate mesoderm. The discussion extends to the continued maturation of the trophoblast into a complex placental support system, detailing the transition from primary to tertiary villi as capillaries connect to the embryonic circulation. Finally, clinical correlates are integrated, explaining how disruptions during this sensitive period can result in severe congenital anomalies such as holoprosencephaly, caudal dysgenesis (sirenomelia), and sacrococcygeal teratomas derived from primitive streak remnants.