Transcription factors Sp8 and Sp9 regulate the development of caudal ganglionic eminence-derived cortical interneurons.

Abstract

Cortical interneurons are derived from the subcortical medial ganglionic eminence (MGE), caudal ganglionic eminence (CGE) and preoptic area (POA). CGE-derived cortical interneurons, which comprise around 30% of all cortical interneurons, mainly express Htr3a, calretinin (CR), Reelin (RELN) and vasoactive intestinal polypeptide (VIP). In the present study, we show that transcription factors Sp8 and Sp9 are co-expressed in the subventricular zone (SVZ) of the dorsal CGE. Conditional knockout of Sp8/9 using the Gsx2-Cre transgenic line results in severe loss of CGE-derived cortical interneurons. We observed migration defects of Sp8/9 double mutant CGE-derived cortical interneurons as they had longer leading processes than controls and they ectopically accumulated in the CGE. Dlx5/6-CIE conditional deletion of Sp8/9 also leads to a significant reduction in the CGE-derived cortical interneurons. We provide evidence that Sp8/9 coordinately regulate CGE-derived cortical interneuron development in part through repressing the expression of Pak3, Robo1, and Slit1. Finally, we show that Cxcl14, a member of the CXC chemokine family, is mainly expressed in CGE-derived interneurons in cortical layers I and II, and its expression is critically dependent on SP8.