Induction of the Neural Crest

California Institute Of Technology, Pasadena CA

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Abstract

DESCRIPTION (provided by applicant): The vertebrate neural crest is a population of migratory cells, arising from the ectoderm, which gives rise to a diverse range of cell types, including most of the peripheral nervous system, melanocytes and the craniofacial skeleton. While many studies have focused on the mechanisms underlying neural crest migration and differentiation, its origins from the ectoderm are less well understood. We have been examining the molecular nature of the neural crest induction and preliminary data suggest that Wnts are both necessary and sufficient to elicit neural crest formation in naive neural tissue. However, other molecules, like BMPs are clearly involved in later events in neural crest formation. These data have led us to formulate a multi-step model for neural crest formation. We hypothesize that: 1) neural crest cells arise by an interaction between neural plate and ectoderm that is mediated by a Wnt signal; 2) the process of induction turns on a discrete set of downstream target genes that render some cells capable of becoming neural crest and leads to expansion of the population; and 3) the decision in the neural folds to become neural crest, neural tube or epidermis may be mediated by interactions amongst cells in the neural folds/dorsal neural tube. To test these hypotheses, the proposed experiments will examine: the molecular basis of the neural crest inducer; the downstream consequences of induction; and how fate decisions are made within the neural folds. Specific experiments will: 1. Further characterize the molecular nature of neural crest induction including the role of Wnt signaling and synergy with other potential inducers. 2. Determine the genes activated by neural crest induction under various conditions and times using array technology. 3. Examine the possible role of Notch signaling in cell fate decisions within the neural folds as cells choose between neural crest, neural tube or epidermal fates.