Pax6Modulates the Dorsoventral Patterning of the Mammalian Telencephalon

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Abstract
ThePax6gene encodes a transcription factor with a restricted expression in the ventricular zone of the pallium and subpallium. We tested whether the function ofPax6is necessary for the correct patterning and morphogenesis of the vertebrate telencephalon. Homozygous embryos of thePax6/Small eyemutant lack functional PAX6 protein because of a point mutation of the gene. In the mutantSmall eyeembryos we detected a ventralization of the molecular patterning of the telencephalon at two borders, the pallium/subpallium and the lateral/medial ganglionic eminence. The results indicate thatPax6controls the lateral limit of the expression ofNkx2.1,Shh,andLhx6in the prechordal neural tube, the telencephalon. This finding is in agreement with previous studies and supports a model for a common genetic mechanism for modulation of the dorsoventral patterning of the prechordal and epichordal CNS. The pattern defects caused by the loss of Pax6 function result in multiple morphological abnormalities in theSmall eyebrain: dysgenesis of the piriform, insular, and lateral cortices, the claustrum–endopiriform nucleus, and a failure in the differentiation of a subpopulation of the cortical precursors. Together the results demonstrate that Pax6 has an essential role for the modulation of the dorsoventral patterning of the embryonic telencephalon, influencing thereby the forebrain morphogenesis.