Dlx1&2 directly promote expression of Cxcl14 to control synapse development and interneuron survival

Dlx genes have fundamental roles in the generation, differentiation, and functions of virtually all forebrain GABAergic neurons. Here we used scRNA-Seq to identify genes that are dysregulated in Dlx1/2 conditional mutants in mouse immature CGE- and MGE-derived cortical and olfactory bulb GABAergic interneurons. Dlx1/2 -regulated genes included Cxcl14 and Nr2f2 that are important for cortical interneuron (CIN) survival. We also identified DLX2-bound putative regulatory elements (pREs) of these Dlx -regulated genes. Within the Dlx -expressing lineage, some DLX-bound pREs were specific to CINs, others appeared to be constitutively bound; the latter class having activity in mature CINs. One such pRE and its associated gene, Cxcl14 , is strongly activated by Dlx1/2 and is essential for synaptogenesis onto CINs.