- Dlx1/2 directly activate Cxcl14, which is essential for synaptogenesis onto cortical interneurons.
- scRNA-Seq of Dlx1/2 conditional mutants revealed dysregulated genes, including Cxcl14 and Nr2f2, that promote cortical interneuron survival.
- DLX2 binds distinct putative regulatory elements, some CIN specific and others constitutively bound with activity persisting in mature CINs.
Proc Natl Acad Sci U S A. 2026 Nov 3;123(44):e2616055123. doi: 10.1073/pnas.2616055123. Epub 2026 Oct 28.
ABSTRACT
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.
PMID:42949953 | DOI:10.1073/pnas.2616055123
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