Distinct cortical interneuron (CIN) subtypes have unique circuit functions; dysfunction in specific subtypes is implicated in neuropsychiatric disorders. Somatostatin (SST) and Parvalbumin (PV) interneurons are the two major subtypes generated by medial ganglionic eminence (MGE) progenitors. Spatial and temporal mechanisms governing their cell-fate specification and differential integration into cortical layers are largely unknown. We provide evidence that Coup-TF1&2 (Nr2f1&2) transcription factor expression in an arc-shaped progenitor domain within the MGE promotes time-dependent survival of this neuroepithelium and the time-dependent specification of layer V SST CINs. Coup-TF1/2 autonomously repress PV+ fate in MGE progenitors, in part through directly driving Sox6 expression. These results have identified a transcriptional pathway controlling SST-PV fate.
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