Abstract
The transcription factor Pax6 controls multiple aspects of forebrain development. Conditional deletion of Pax6 in embryonic mouse cortex causes increased proliferation of cortical progenitor cells and a concomitant decrease in neural differentiation. Notch signaling regulates the balance between proliferation and differentiation of cortical progenitor cells, suggesting a possible connection between Pax6 and Notch signaling. We investigated how expression of the Notch ligand delta-like 1 (Dll1) is altered by loss of Pax6. Acute cortex-specific deletion of Pax6 resulted in a widespread decrease in the density of Dll1+ cells at embryonic days 12.5 and 13.5 (E12.5 and E13.5). In constitutive loss-of-function mutants, decreases in the densities of Dll1+ cells were more limited both spatially and temporally. Controlled over-expression of Pax6 had no detectable effect on Dll1 expression. The proneural transcription factor Neurog2 is a target of Pax6 that can activate Dll1 expression and we found clear co-expression of Neurog2 and Dll1 in radial glial progenitors, suggesting that Pax6's effect on Dll1 could be mediated through Neurog2. However, we found no change in Dll1+ cells in Neurog2 -/- cortex suggesting either that Neurog2 is not directly involved, or that its loss of function in embryonic cortex can be compensated for.