{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T10:08:54Z","timestamp":1792145334437,"version":"4.4.0"},"reference-count":58,"publisher":"The Company of Biologists","issue":"18","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,9,15]]},"abstract":"<jats:p>Dlx homeobox genes play a crucial role in the migration and differentiation of the subpallial precursor cells that give rise to various subtypes of \u03b3-aminobutyric acid (GABA)-expressing neurons of the forebrain, including local-circuit cortical interneurons. Aberrant development of GABAergic interneurons has been linked to several neurodevelopmental disorders, including epilepsy, schizophrenia, Rett syndrome and autism. Here, we report in mice that a single-nucleotide polymorphism (SNP) found in an autistic proband falls within a functional protein binding site in an ultraconserved cis-regulatory element. This element, I56i, is involved in regulating Dlx5\/Dlx6 homeobox gene expression in the developing forebrain. We show that the SNP results in reduced I56i activity, predominantly in the medial and caudal ganglionic eminences and in streams of neurons tangentially migrating to the cortex. Reduced activity is also observed in GABAergic interneurons of the adult somatosensory cortex. The SNP affects the affinity of Dlx proteins for their binding site in vitro and reduces the transcriptional activation of the enhancer by Dlx proteins. Affinity purification using I56i sequences led to the identification of a novel regulator of Dlx gene expression, general transcription factor 2 I (Gtf2i), which is among the genes most often deleted in Williams-Beuren syndrome, a neurodevelopmental disorder. This study illustrates the clear functional consequences of a single nucleotide variation in an ultraconserved non-coding sequence in the context of developmental abnormalities associated with disease.<\/jats:p>","DOI":"10.1242\/dev.051052","type":"journal-article","created":{"date-parts":[[2010,8,12]],"date-time":"2010-08-12T01:11:05Z","timestamp":1281575465000},"page":"3089-3097","source":"Crossref","is-referenced-by-count":71,"title":["An SNP in an ultraconserved regulatory element affects <i>Dlx5\/Dlx6<\/i> regulation in the forebrain"],"prefix":"10.1242","volume":"137","author":[{"given":"Luc","family":"Poitras","sequence":"first","affiliation":[{"name":"Center for Advanced Research in Environmental Genomics (CAREG), Department of Biology, University of Ottawa, Ottawa, ON K1N 6N5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man","family":"Yu","sequence":"additional","affiliation":[{"name":"Center for Advanced Research in Environmental Genomics (CAREG), Department of Biology, University of Ottawa, Ottawa, ON K1N 6N5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cindy","family":"Lesage-Pelletier","sequence":"additional","affiliation":[{"name":"Center for Advanced Research in Environmental Genomics (CAREG), Department of Biology, University of Ottawa, Ottawa, ON K1N 6N5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan B.","family":"MacDonald","sequence":"additional","affiliation":[{"name":"Center for Advanced Research in Environmental Genomics (CAREG), Department of Biology, University of Ottawa, Ottawa, ON K1N 6N5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Philippe","family":"Gagn\u00e9","sequence":"additional","affiliation":[{"name":"Centre de Recherche du CHUQ-CHUL, Faculty of Medicine, Laval University, QC G1V 4G2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Hatch","sequence":"additional","affiliation":[{"name":"Center for Advanced Research in Environmental Genomics (CAREG), Department of Biology, University of Ottawa, Ottawa, ON K1N 6N5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Kelly","sequence":"additional","affiliation":[{"name":"Proteomics Platform of the Qu\u00e9bec Genomic Center, Centre de Recherche du CHUQ-CHUL, Laval University, QC G1V 4G2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven P.","family":"Hamilton","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of California, San Francisco, CA 94158-2324, USA"},{"name":"Institute for Human Genetics, University of California, San Francisco, CA 94158-2324, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John L. 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