Although Sox1, Sox2, and Sox3 are all part of the Sox-B1 group of transcriptional regulators, only Sox1 appears to play a direct role in neural cell fate determination and differentiation. We find that overexpression of Sox1 but not Sox2 or Sox3 in cultured neural progenitor cells is sufficient to induce neuronal lineage commitment. Sox1 binds directly to the Hes1 promoter and suppresses Hes1 transcription, thus attenuating Notch signaling. Sox1 also binds to beta-catenin and suppresses beta-catenin-mediated TCF/LEF signaling, thus potentially attenuating the wnt signaling pathway. The C-terminus of Sox1 is required for both of these interactions. Sox1 also promotes exit of cells from cell cycle and up-regulates transcription of the proneural bHLH transcription factor neurogenin 1 (ngn1). These observations suggest that Sox1 works through multiple independent pathways to promote neuronal cell fate determination and differentiation.