The specific aims are to analyze mechanisms involved in normal and abnormal closure of the neural tube in mutant mice which exhibit neural dysraphism. Alterations in the cell surface and shape of neuroepithelial cells, as well as interactions between the neuroepithelial cells and adjacent chordamesodermal cells via the neural basal lamina will be studied by a variety of techniques, including immunocytochemistry and cytochemistry at the ultrastructural level, immunofluorescence histochemistry, scanning electron microscopy, and autoradiography. The expression of mutant genes in producing neural tube defects will be analyzed by low doses of retinoic acid, folic acid antagonists, and hydroxyurea. This project will help to contribute to an understanding of the etiology of specific human neurological disorders such as exencephaly, meningocele, anencephaly, and spina bifida.
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