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.
Authors
- Alex S. Nord (ORCID: https://orcid.org/0000-0003-4259-7514)
- Susan Lindtner (ORCID: https://orcid.org/0009-0001-9045-318X)
- John L.R. Rubenstein (ORCID: https://orcid.org/0000-0002-4414-7667)
- Cindy T. J. van Velthoven (ORCID: https://orcid.org/0000-0001-5120-4546)
- Jia Sheng Hu (ORCID: https://orcid.org/0000-0002-2530-2051)
- Emily Ling-Lin Pai (ORCID: https://orcid.org/0000-0002-6967-5239)
- Yurong Wang (ORCID: https://orcid.org/0000-0003-1140-0256)
- Athéna Rebecca Ypsilanti (ORCID: https://orcid.org/0000-0002-0310-7693)
- Siavash Fazel Darbandi
- Teng Guo
Institutions
- Allen Institute for Brain Science (US)
- University of California, Davis (US)
Publication Details
- Journal
- Proceedings of the National Academy of Sciences
- Published
- 2026-10-28
- DOI
- https://doi.org/10.1073/pnas.2616055123
- Primary Topic
- Neurogenesis and neuroplasticity mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Institute of Mental Health
- National Institute of General Medical Sciences