description): The long term objective of this research is to gain insight into how central nervous system development is regulated at the molecular and cellular level. The Wnt-1 gene encodes a signaling molecule which is first expressed in the neural plate and has been shown, by mutational analysis in the mouse, to be essential for midbrain development. The central hypothesis of this proposal is that transcription factors responsible for activation of Wnt-1 are themselves key developmental regulators of the CNS. In the studies proposed, the regulation of Wnt-1 will be examined using transgenic mouse and cell culture techniques.