Removal of Pax6 Partially Rescues the Loss of Ventral Structures in Shh Null Mice

Pax6 and Gli3 are dorsally expressed genes that are known to antagonize sonic hedgehog (Shh) activity. We have previously shown that dorsoventral patterning defects seen in Shh(-/-) mutants are rescued in Shh(-/-);Gli3(-/-) compound mutants. Here we investigate if the loss of Pax6 can also ameliorate defects seen in Shh(-/-) mutants. In support of this notion, we observe that the fusion of the cerebral vesicles seen in Shh(-/-) mutants is partially corrected in E12.5 Shh(-/-);Pax6(-/-) compound mutants. Investigation of pan-ventral markers such as Dlx2 also shows that, unlike Shh(-/-), a broad domain of expression of this gene is observed in Shh(-/-);Pax6(-/-) mice. Interestingly, we observe that while the expression of ER81 in the ventral telencephalon is expanded, the expression of Ebf1 is lost. This suggests that the rescued ventral domain observed in Shh(-/-);Pax6(-/-) mice is the dorsal lateral ganglionic eminence region. With regard to dorsal telencephalic patterning, we also observe rescue of the pallial-subpallial boundary, as well as a partial rescue of the dorsal midline. Together, our findings are consistent with Pax6 function being required for aspects of Gli3-mediated telencephalic patterning.