Figure 1. Midsagittal illustrations showing development of the blastocyst. A: Continued proliferation of cells produces a sphere containing a blastocystic cavity surrounded by an eccentrically located inner cell mass and a surrounding ring of trophoblast cells. B: The inner cell mass develops further into a two-layered structure, the blastodisc, containing the epiblast adjacent to the amnionic cavity and the hypoblast adjacent to the yolk sac. C: With further development, the blastodisc thickens cranially to form the prochordal plate.
Figure 2. Normal human gastrulation. Upper: Prospective endo- and mesodermal cells of the epiblast migrate toward the primitive streak and ingress (arrows) through the primitive groove to become the definitive endoderm and mesoderm. Lower: Prospective notochordal cells in the cranial margin of the Hensen node will ingress through the primitive pit (arrows) during primitive streak regression to become the notochordal process.
Figure 3. Location of prospective neuroepithelium. Seen here is a dorsal view of an avian embryo during gastrulation. The striped region illustrates localization by earlier mapping studies involving carbon particles; hatched area illustrates additional caudal areas demonstrated by more recent mapping studies using horseradish peroxidase injections and chimeric transplantation.
Figure 4. Formation of the notochord in avian embryos. The notochord is formed through the addition of cells to its caudal end as the primitive streak regresses; true cranial growth of the notochord is minimal.
Figure 5. Illustrations showing notochordal canalization, intercalation, and excalation. A: The notochordal process contains a central lumen (the notochordal canal), which is continuous with the amnionic cavity through the primitive pit. B: During intercalation, the canalized notochordal process fuses with the underlying endoderm; the communication of the amnion with the yolk sac forms the primitive neurenteric canal (arrows). C: During excalation, the notochord rolls up and separates from the endoderm to become the definitive notochord; the primitive neurenteric canal becomes obliterated (arrows).
Figure 6. Depiction of various waves of neural tube closure in human embryos. There are thought to be at least five waves of closure in normal human embryogenesis. Anencephaly is thought to represent failure of Wave 2, myelomeningocele a failure at the junction of Waves 4 and 5 (representing the junction of primary and secondary neurulation). From Gilbert SF, 2003.
Figure 7. Secondary neurulation. Upper illustration depicts secondary neurulation in avian embryos. A: The medullary cord consists of multiple lumina, each surrounded by an outer layer of tightly packed, radially oriented cells and containing an inner group of more loosely packed cells. B: Adjacent cords coalesce to form larger aggregates; simultaneously, the inner cells are lost. Eventually a single structure is formed, having a single lumen that is not yet in direct communication with the lumen formed by primary neurulation. C: Later, the neural tube formed by secondary neurulation (2° NT) fuses with that formed from primary neurulation (1° NT); at this point, the lumina of the two neural tubes communicate directly. Lower illustration depicts secondary neurulation in mouse embryos. A medullary rosette is composed of cells radially arranged about an empty central lumen. The lumen is always in communication with the central canal formed by primary neurulation. Growth of the secondary neural tube occurs by additional cavitation of the secondary lumen and by recruiting additional cells from the CCM. NC = notochord.
Figure 8. Ascent of the conus medullaris. AD: Illustrations demonstrating progressive ascent of the conus medullaris during embryogenesis and the immediate postnatal period. (A, 8 weeks' gestation; B, 24 weeks' gestation; C, newborn; and D, adulthood. (From Moore KL, 1982). E: Vertebral level of termination of the conus medullaris during fetal and early postnatal life. Adapted from Chatkupt, Chatkupt, and Johnson, 1993.
Figure 9. Morphogenetics and biomechanics of neural plate bending. A: Formation of neural folds from neuroepithelium and adjacent cutaneous ectoderm (presumptive epidermis). The transition zone will give rise to the neural crest cells and their derivatives. B: Formation of the MHP or neural groove, and elevation of the neural folds. Note the wedging of the midline neuroepithelial cells immediately dorsal to the notochord (inset). C: Formation of the DLHP and convergence of the neural folds in preparation for neural fold fusion (From Gilbert SF, 1997).
Figure 10. Interactions of Sonic hedgehog and Wingless to establish metameric patterning between adjacent cells in Drosophila embryos. Ci = cubitus interruptus; DPP = decapentaplegia.
Figure 11. Embryogenetic theory for the origin of some myelomeningoceles, hemimyelomeningoceles, SCMs, and other complex dysraphic malformations. According to this theory, the Hensen node is altered resulting in disrupted midline axial integration during gastrulation. Two heminotochords are laid down and the surrounding neural plate is induced to form two relatively independent hemineural tubes. The intervening cells derived from multipotent cells in the Hensen node can develop into a variety of both normal and abnormal tissues between the two resultant hemicords such as neurenteric cysts, ectopic ovarian or renal tissues, Wilm tumor or teratomas (all reported in the literature). From Luo and Nye, 2001.
Figure 12. The homocysteine/methionine cycle. The conversion of homocysteine to methionine is mediated by the donation of a methyl group from 5-methyltetrahydrofolate (5-Me tetrahydrofolate); in the process, tetrahydrofolate is formed. This reaction is catalyzed by the enzyme methionine synthase and uses cobalamin (vitamin B12) as a coenzyme. The 5-methyletrahydrofolate is regenerated from tetrahydrofolate by using 5,10-methylenetetrahydrofolate (510 Me Tetrahydrofolate) as an intermediary, completing a folate cycle. Methionine is subsequently used as a methyl (CH3) donor in various important metabolic reactions and is converted to homocysteine in the process. SAH = S-adenosylhomocysteine; SAM = S-adenosylmethionine.