Sonic hedgehog signaling confers ventral telencephalic progenitors with distinct cortical interneuron fates.

Interneurons in the cerebral cortex regulate cortical functions through the actions of distinct subgroups that express parvalbumin, somatostatin, or calretinin. The genesis of the first two subgroups requires the expression of NKX2.1, which is maintained by SHH signaling during neurogenesis. In this paper, we report that mosaic elimination in the medial ganglionic eminence (MGE) of Smo, a key effector of SHH signaling, reveals that MGE progenitors retain a remarkable degree of plasticity during the neurogenic period. SHH signaling prevents the upregulation of GSX2 and conversion of some MGE progenitors to a caudal ganglionic eminence-like, bipolar calretinin-expressing cell fate that is promoted by GSX2. In addition, a higher level of SHH signaling promotes the generation of the somatostatin-expressing interneuron at the expense of parvalbumin-expressing subgroup. These results indicate that cortical interneuron diversity, a major determinant of cortical function, is critically influenced by differential levels of SHH signaling within the ventral telencephalon.