Birth defects of the CNS such as anencephaly and spina bifida are among the most severe and at the same time poorly understood conditions which may affect an infant. While there is considerable information on the morphological characteristics of these defects, there is little data on the mechanisms which produce them. The goal of the current study is to determine the composition and role of the neuroepithelial basal lamina (BL) in neurulation, where it may provide important spatial and temporal cues and may determine the shape, orientation and polarity of neuroepithelial cells. EM immunocytochemical localization of BL components (fibronectin, laminin, collagens, proteoglycan) during neurulation will be carried out and correlated with regional morphogenesis using computer-assisted three-dimensional reconstructions. Because of its susceptibility to neural tube defects, the zone of fusion between primary and secondary neural tubes will be examined in detail in early human and normal mouse embryos. Similar observations will be made on the maturation of the BL in neurological mutants with a high spontaneous incidence of defects of cephalic (Splotch) or lumbosacral (delayed Splotch) neural tube closure. Other embryos will be exposed in whole embryo culture to agents which specifically alter the synthesis or deposition of BL components and resulting morphological changes correlated with alterations in BL constituents. This combined approach should allow precise correlation of developmental changes in BL composition to morphogenesis of the neuraxis in human and normal mouse as well as neurological mutant and teratogen-treated embryos. The results of these experiments should elucidate not only the role of the BL in neurulation, but at the same time should produce valuable new data on the pathogenesis of developmental defects of the nervous system.
