Sonic hedgehog is required for the induction of ventral cell types in the neural tube, and in recent years for rapid progress has been made in understanding the signaling pathway for sonic hedgehog. Using Xenopus laevis as a model, the Principal Investigator's groups has shown that Gli genes, which encode zinc finger transcription factors with transient and graded expression in the neural plate or neural tube, are involved in this process. Specifically, Gli1 has been found to be necessary and sufficient for floor plate and ventral neuronal differentiation, whereas Gli2 and Gli3 appear to antagonize the effect of Gli1. In further studies of the roles of Gli genes in sonic hedgehog signaling and development of the neural tube, the Principal Investigator proposes several important and ambitious studies. He proposed to analyze the tissue and cellular localization of the Gli1 gene products, to carry out a structure/function analysis of gli proteins using site- directed mutagenesis, to make Gli1 or Gli3 transgenic mice as a natural extension of the frog studies, to further analyze the antagonize Gli1 function in the frogs, and finally to determine if Gli3 is required for dorsal neural tube cell determination.
