{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T19:59:04Z","timestamp":1760385544420,"version":"3.41.2"},"reference-count":32,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,2,9]],"date-time":"2017-02-09T00:00:00Z","timestamp":1486598400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002597","name":"Kyung Hee University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002597","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genesis"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>The sine oculis homeobox protein Six3 plays pivotal roles in the development of the brain and craniofacial structures. In humans, <jats:italic>SIX3<\/jats:italic> haploinsufficiency results in holoprosencephaly, a defect in anterior midline formation. Although much is known about the evolutionarily conserved functions of <jats:italic>Six3<\/jats:italic>, the regulatory mechanism responsible for the expression pattern of <jats:italic>Six3<\/jats:italic> remains relatively unexplored. To understand how the transcription of <jats:italic>Six3<\/jats:italic> is controlled during embryogenesis, we screened \u223c300 kb of genomic DNA encompassing the <jats:italic>Six3<\/jats:italic> locus for <jats:italic>cis<\/jats:italic>\u2010acting regulatory elements capable of directing reporter gene expression to sites of <jats:italic>Six3<\/jats:italic> transcription in transgenic mouse embryos. We identified a novel enhancer element, whose activity recapitulates endogenous <jats:italic>Six3<\/jats:italic> expression in the ventral midbrain, pretectum, and thalamus. Cross\u2010species comparisons revealed that this <jats:italic>Six3<\/jats:italic> brain enhancer is functionally conserved in other vertebrates. We also showed that normal <jats:italic>Six3<\/jats:italic> transcription in the ventral midbrain and pretectum is dependent on <jats:italic>Ascl1<\/jats:italic>, a basic helix\u2010loop\u2010helix proneural factor. Moreover, loss of <jats:italic>Ascl1<\/jats:italic> resulted in downregulation of the <jats:italic>Six3<\/jats:italic> brain enhancer activity, emphasizing its unique role in regulating <jats:italic>Six3<\/jats:italic> expression in the developing brain.<\/jats:p>","DOI":"10.1002\/dvg.23017","type":"journal-article","created":{"date-parts":[[2017,1,17]],"date-time":"2017-01-17T06:16:44Z","timestamp":1484633804000},"source":"Crossref","is-referenced-by-count":4,"title":["<scp>I<\/scp>dentification of a conserved <i>cis<\/i>\u2010regulatory element controlling mid\u2010diencephalic expression of mouse <i>Six3<\/i>"],"prefix":"10.1002","volume":"55","author":[{"given":"Bumwhee","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Genetic Engineering, College of Life Sciences and Graduate School of Biotechnology Kyung Hee University Yongin\u2010si 446\u2010701 Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiyeon","family":"Yoon","sequence":"additional","affiliation":[{"name":"Department of Genetic Engineering, College of Life Sciences and Graduate School of Biotechnology Kyung Hee University Yongin\u2010si 446\u2010701 Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Duc","family":"Tri Lam","sequence":"additional","affiliation":[{"name":"Department of Genetic Engineering, College of Life Sciences and Graduate School of Biotechnology Kyung Hee University Yongin\u2010si 446\u2010701 Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaeseung","family":"Yoon","sequence":"additional","affiliation":[{"name":"Department of Genetic Engineering, College of Life Sciences and Graduate School of Biotechnology Kyung Hee University Yongin\u2010si 446\u2010701 Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kwanghee","family":"Baek","sequence":"additional","affiliation":[{"name":"Department of Genetic Engineering, College of Life Sciences and Graduate School of Biotechnology Kyung Hee University Yongin\u2010si 446\u2010701 Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0008-9928","authenticated-orcid":false,"given":"Yongsu","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Genetic Engineering, College of Life Sciences and Graduate School of Biotechnology Kyung Hee University Yongin\u2010si 446\u2010701 Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,2,9]]},"reference":[{"key":"e_1_2_2_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21094"},{"key":"e_1_2_2_3_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.067660"},{"key":"e_1_2_2_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn874"},{"key":"e_1_2_2_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1350"},{"key":"e_1_2_2_6_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.129.17.4057"},{"key":"e_1_2_2_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20295"},{"key":"e_1_2_2_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02292"},{"key":"e_1_2_2_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-2-8"},{"key":"e_1_2_2_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2008.07.003"},{"key":"e_1_2_2_11_1","article-title":"Six3 dosage mediates the pathogenesis of holoprosencephaly","author":"Geng 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