A Presidential Young Investigator Award will support studies to define molecular mechanisms involved in neuronal differentiation. Cell lines derived from cerebellar granule neurons and the embryonic carcinoma cell line, P19, will be used for subtractive hybridization studies to begin to identify genes that are specifically expressed in differentiated or undifferentiated cells. Cloning of homologous genes will be used to identify other genes important to differentiation. Gene transfection will be used to study function of those genes identified. In addition, factors involved in transcriptional regulation of GAP-43, a neuron-specific gene protein, will be identified. These studies are fundamental to understanding the mechanisms underlying brain development.