MIGUEL AND ISMAEL

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IN NEW YORK THERE ARE LOTS
OF SPORT CENTRES

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Progress in understanding the molecular basis of primary neurulation has occurred on two fronts: neural induction and shaping and bending of the neural plate. In regard to the former, the neural plate is now known to be the default state of the ectoderm, and induction of the neural plate actually involves suppressing the formation of the epidermal ectoderm (neural induction is not considered further herein). In regard to shaping and bending of the neural plate, about 100 mutations in the mouse have been identified that result in defective shaping and/or bending and, consequently, result in neural tube defects (NTDs); thus, these mutations provide insight into which genes are involved in both normal and abnormal neurulation. Because these form-shaping events of neurulation are driven by changes in cell behavior, as discussed earlier, it is not surprising that mutation of cytoskeletal, extracellular matrix/cell adhesion, cell cycle, and cell death genes results in NTDs. Neurulation is a highly choreographed morphogenetic series of events that must be precisely timed and coordinated across multiple tissues. This presumably involves signaling among tissues. It is the hope of studies using mouse mutations that such signaling pathways will be identified, ultimately leading to an understanding of the molecular basis of neurulation and the formation of NTDs in both animal models and ultimately in humans. In the following sections, we discuss what has been learned about the molecular basis of shaping and bending of the neural plate.Embryology Neurulation is the critical morphogenetic event occurring during the fourth week of human gestation, converting the previously developed neural plate into the ectoderm covered neural tube that will eventually differentiate into the brain and spinal cord. Genetic regulation of the events involved in mammalian neural tube morphogenesis is a complicated process that involves a multitude of genes. These genes have vital functions in a range of biological activities that are thought to include signaling molecules, transcription proteins and factors, cytoskeletal and gap junction proteins, growth factors, and tumor suppressor genes (Copp et al., 2003; Ewart et al., 1997; Sah et al., 1995; Zhang et al., 1996). The neural tube, formed by the cell shape changes and movements, ultimately fuses at several discrete points.Neurulation (or primary neurulation) starts in the fourth week of gestation and is the process that leads to the formation of the neural tube from the neural plate, the rudiment of the CNS [34]. It encompasses four essential and overlapping events: (1) neural induction, (2) shaping, (3) bending of the neural plate, and (4) closure of the neural tube. Neural induction (1) is the process of neural plate formation, that is, the beginning of the development of the CNS. It occurs during gastrulation starting on day 18. As described earlier, cells of the ectoderm differentiate into the neuroectoderm, a pseudostratif.

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