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Publication : Positive autoregulation of Sox17 is necessary for gallbladder and extrahepatic bile duct formation.

First Author  Trinh LT Year  2025
Journal  Development Volume  152
Issue  2 PubMed ID  39745200
Mgi Jnum  J:360569 Mgi Id  MGI:7840308
Doi  10.1242/dev.203033 Citation  Trinh LT, et al. (2025) Positive autoregulation of Sox17 is necessary for gallbladder and extrahepatic biliary duct formation. Development :dev.203033
abstractText  Expression of SRY-box transcription factor 17 (Sox17) in the endodermal region caudal to the hepatic diverticulum during late gastrulation is necessary for hepato-pancreato-biliary system formation. Analysis of an allelic series of promoter-proximal mutations near the transcription start site (TSS) 2 of Sox17 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&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&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&EHBD system, impairing or preventing development.
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