New insight into human neurological diseases has emerged from investigation of normal pathways of brain development. Dr. Rowitch’s laboratory investigates Sonic hedgehog (Shh) signaling in regulation of neural stem cell proliferation and specification and the critical roles played by downstream transcription factors. During postnatal brain development, Sonic hedgehog (Shh) functions as potent mitogen for cerebellar granule neuron precursors (CGNP). Dr. Rowitch’s research has established that N-myc and D-type cyclins are amongst the common targets of Shh signaling in CGNP and medulloblastoma, and he has used global measures of gene expression to further validate the relationship between brain development and tumorigenesis. In the embryonic neural tube, Shh is essential for development of oligodendrocytes. Work of Dr. Rowitch and colleagues has shown that activation of Olig genes is a critical component of oligodendrocyte specification from neural stem cells. We are currently investigating roles for Olig genes in CNS tumorigenesis, multiple sclerosis and newborn neurological injury. Finally, we have shown that the bHLH protein SCL is a regulator of astrocyte specification through cross-antagonistic interactions with Olig2. This finding supports the proposal that astrocyte generation is heterogeneous and occurs in restricted regions of the developing CNS.