Neural induction is the first step in the genesis of the vertebrate nervous system and one of best known examples of how embryonic cells are assigned a particular cell fate during vertebrate development. The cellular aspects of neural induction were revealed in the early 1900's by embryologists studying amphibian embryos. These studies showed that neural induction occurs when ectoderm comes in contact with dorsal mesoderm during gastrulation. Uninduced ectoderm gives rise to epidermal tissue while the ectoderm that interacts with the inducer gives rise to neural tissue by initially forming the neural plate. These studies established induction as the cellular mechanism for specifying ectoderm to form neural tissue and subsequent studies were initiated to study the molecular basis of this assignment. In spite of these studies, however, very little is known about the molecular nature of the inducer nor what molecular changes occur in ectoderm that promote neural rather than epidermal differentiation. One new approach to the problem of neural induction is based on our observation that the transcriptional activation of neural cell adhesion molecule (N-CAM) RNA is a early response of ectoderm to neural induction in Xenopus embryos. This observation suggests that neural induction can be studied as a problem in gene expression and function by the following types of experiments: (1) The inducer produced by dorsal mesoderm will be characterized using the induction of N-CAM RNA expression in ectoderm as an assay. Because this assay measures an early response of ectoderm to induction, it will allow a direct study of the developmental expression of the inducer and its basic chemical properties. (2) N- CAM expression in the neural plate is consistent with the model that N-CAM has a function in early neural development. N-CAM gene function will be studied using gene transfer to disrupt N- CAM expression during neural plate formation and morphogenesis. (3) Other genes by analogy to N-CAM expression during neural plate formation and morphogenesis. (3) Other genes by analogy to N-CAM could be transcriptionally activated in ectoderm as an early consequence of induction. cDNA libraries will be screened with a variety of hybridization probes to isolate other genes of this class. This proposed experiments focus on the genes transcriptionally activated in ectoderm following neural induction. By focusing on the expression and function of genes with these properties, it may be possible to isolate and characterize molecules needed by embryonic cells to undergo neural development. Identifying the molecules involved and understanding how they work is one step towards eventually understanding the embryonic processes that shape the early nervous system. Such an understanding is a prerequisite to manipulating the regeneration of neural tissue in a clinical setting.
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