Sox21 regulates the progression of neuronal differentiation in a dose-dependent manner.

Members of the SoxB transcription factor family play critical roles in the regulation of neurogenesis. The SoxB1 proteins are required for the induction and maintenance of a proliferating neural progenitor population in numerous vertebrates, however the role of the SoxB2 protein, Sox21, is less clear due to conflicting results. To clarify the role of Sox21 in neurogenesis, we examined its function in the Xenopus neural plate. Here we report that misexpression of Sox21 expands the neural progenitor domain, and represses neuron formation by binding to Neurogenin (Ngn2) and blocking its function. Conversely, we found that Sox21 is also required for neuron formation, as cells lacking Sox21 undergo cell death and thus are unable to differentiate. Together our data indicate that Sox21 plays more than one role in neurogenesis, where a threshold level is required for cell viability and normal differentiation of neurons, but a higher concentration of Sox21 inhibits neuron formation and instead promotes progenitor maintenance.