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Furthermore, loss-of-function mutations in mouse cycling genes result in segmentation anomalies, including misplaced somitic boundaries and malformations of the vertebral column and ribs. In some individuals, caudal malformations are associated with more cranial abnormalities. One of these associations is called the VATER association because it includes some or all of the following anomalies: A number of other syndromes may be related to these associations.
Although the anomalies found in these associations are diverse, it is believed that they all arise from defects resulting from abnormal growth and migration during gastrulation. Mesodermal structures formed during the 3rd and 4th weeks participate in the development of most of the structures involved in caudal dysplasia and associated malformations.
Embriología humana – William D. Larsen – Google Books
For example, the sacral and coccygeal vertebrae form from structures called sclerotomes that develop from the sacral and caudal somites discussed in Ch. The intermediate mesoderm differentiates into kidneys in response to induction by the ingrowing mesoderm ureteric buds discussed in Ch.
Imperforate anus may result from the improper migration of caudal mesodermal in relation to the forming anal membrane discussed in Ch.
embriologiaa Radial forearm malformations apparently result from anomalous migration and differentiation of lateral plate mesoderm discussed in Ch. In animal models, caudal dysplasia can be induced by both environmental factors and mutations. Severe reduction of caudal structures has resulted in fusion of the lower limb buds. Shown is Milagros Cerron at about 1 year of age with her physician.
Formation of the neural plate is induced by the primitive node, the human equivalent of the organizer discussed early in the ebriologia. Thus, the process of neural plate forma- tion is called neural induction.
As a result of neural induction, ectodermal cells differentiate into a thick plate of pseudostratified, columnar neuroepithelial cells neuroectoderm. The neural plate forms first at the cranial embrkologia of the embryo and then differentiates in a cranial-to-caudal direction. As described in Chapter embriologua, the neural plate folds during the 4th week to form a neural tube, the precursor of the central nervous system.
The lateral lips of the neural plate also give rise to an extremely important population of cells, neural crest cells, which detach during for- mation of the neural tube and migrate in the embryo to form a variety of structures.
The neural plate is broad cranially and tapered caudally.
The expanded cranial portion gives rise to brain. Even at this very early stage of differentia- tion, the presumptive brain is visibly divided into three regions: The narrower caudal portion of embriologiz neural plate continuous cranially with the hindbrain gives rise to the spinal cord.
Eventually, this level of the developing nervous system will be flanked by somites. The notochord lies in the midline just deep to the neural plate.
It extends cranially from the primitive node to end near the future juncture between the forebrain and midbrain. Similar defects are also observed in mice with mutations in the Brachyury gene, a T-box—containing transcription factor expressed throughout the primitive streak embriiologia gastrulation Fig. Analysis of such mice indicates that the mutation interferes with gastrulation by preventing the normal ingression of epiblast cells through the primitive streak, embriolkgia providing insight into how widespread mesodermal anomalies could result in humans with caudal dysplasia.
In situ hybridization showing localization of chick Brachyury mRNA, a T-box—containing transcription factor, which is expressed throughout the primitive streak. Recall that the Nieuwkoop center induces the organizer, which patterns the mesoderm in the dorsal-ventral plane. In addition, the organizer induces the neural plate. Although the location of the Nieuwkoop center is well established in amphibians, its location is birds and mammals remains uncertain.
Schematic sequence showing growth of the neural plate and regression of the primitive streak between day 18 and day The primitive streak shortens only slightly, but it occupies a progressively smaller proportion of the length of the embryonic disc as the neural plate and embryonic disc grow.
Scanning electron micrograph of a Macaque embryo compa- rable to a day human embryo. The neural plate is clearly visible, and the expansions that will become the major subdivisions of the brain are appar- ent arrows. Only a small region of the primitive streak remains.
The prim- itive streak will disappear on day Nevertheless, loss-of-function experiments in mouse suggest that similar.