AUTHOR=Dorà Elena , Price David J. , Mason John O. 

TITLE=Loss of Pax6 Causes Regional Changes in Dll1 Expression in Developing Cerebral Cortex

JOURNAL=Frontiers in Cellular Neuroscience

VOLUME=13

YEAR=2019

URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2019.00078

DOI=10.3389/fncel.2019.00078

ISSN=1662-5102

ABSTRACT=<p>The transcription factor Pax6 controls multiple aspects of forebrain development. Conditional deletion of <italic>Pax6</italic> 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 <italic>delta-like 1</italic> (<italic>Dll1</italic>) is altered by loss of Pax6. Acute cortex-specific deletion of Pax6 resulted in a widespread decrease in the density of <italic>Dll1</italic>+ 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 <italic>Dll1</italic>+ cells were more limited both spatially and temporally. Controlled over-expression of Pax6 had no detectable effect on <italic>Dll1</italic> expression. The proneural transcription factor Neurog2 is a target of Pax6 that can activate <italic>Dll1</italic> expression and we found clear co-expression of <italic>Neurog2</italic> and <italic>Dll1</italic> in radial glial progenitors, suggesting that Pax6’s effect on <italic>Dll1</italic> could be mediated through Neurog2. However, we found no change in <italic>Dll1</italic>+ cells in <italic>Neurog2</italic><sup>−/−</sup> cortex suggesting either that Neurog2 is not directly involved, or that its loss of function in embryonic cortex can be compensated for.</p>