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Analysis of an allelic series of promoter-proximal mutations near the transcription start site (TSS) 2 of Sox17 in mouse has revealed that gallbladder (GB) and extrahepatic bile duct (EHBD) development is exquisitely sensitive to Sox17 expression levels. Deletion of a SOX17-binding cis-regulatory element in the TSS2 promoter impairs GB and EHBD development by reducing outgrowth of the nascent biliary bud. These findings reveal the existence of a SOX17-dependent autoregulatory loop that drives Sox17 expression above a critical threshold concentration necessary for GB and EHBD development to occur, and that minor impairments in Sox17 gene expression are sufficient to impair the expression of SOX17-regulated genes in the nascent GB and EHBD system, impairing or preventing development.<\/jats:p>","DOI":"10.1242\/dev.203033","type":"journal-article","created":{"date-parts":[[2025,1,2]],"date-time":"2025-01-02T13:41:38Z","timestamp":1735825298000},"source":"Crossref","is-referenced-by-count":1,"title":["Positive autoregulation of <i>Sox17<\/i> is necessary for gallbladder and extrahepatic bile duct formation"],"prefix":"10.1242","volume":"152","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9394-1648","authenticated-orcid":false,"given":"Linh T.","family":"Trinh","sequence":"first","affiliation":[{"name":", Vanderbilt University 1 Center for Stem Cell Biology , Nashville, TN 37232 ,","place":["USA"]},{"name":"Vanderbilt University 2 Department of Cell and Developmental Biology , , Nashville, TN 37232 ,","place":["USA"]},{"name":"Vanderbilt University 3 Program in Developmental Biology , , Nashville, TN 37232 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan R.","family":"Finnel","sequence":"additional","affiliation":[{"name":", Vanderbilt University 1 Center for Stem Cell Biology , Nashville, TN 37232 ,","place":["USA"]},{"name":"Vanderbilt University 2 Department of Cell and Developmental Biology , , Nashville, TN 37232 ,","place":["USA"]},{"name":"Vanderbilt University 3 Program in Developmental Biology , , Nashville, TN 37232 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9513-2262","authenticated-orcid":false,"given":"Anna B.","family":"Osipovich","sequence":"additional","affiliation":[{"name":", Vanderbilt University 1 Center for Stem Cell Biology , Nashville, TN 37232 ,","place":["USA"]},{"name":"Vanderbilt University 4 Department of Molecular Physiology and Biophysics , , Nashville, TN 37232 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica R.","family":"Musselman","sequence":"additional","affiliation":[{"name":"5 School of Arts and Sciences, Vanderbilt University, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2523-7616","authenticated-orcid":false,"given":"Leesa L.","family":"Sampson","sequence":"additional","affiliation":[{"name":", Vanderbilt University 1 Center for Stem Cell Biology , Nashville, TN 37232 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9260-4009","authenticated-orcid":false,"given":"Christopher V. 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