1. Positive autoregulation of Sox17 is necessary for gallbladder and extrahepatic bile duct formation.
- Author
-
Trinh LT, Finnel RR, Osipovich AB, Musselman JR, Sampson LL, Wright CVE, and Magnuson MA
- Subjects
- Animals, Mice, HMGB Proteins metabolism, HMGB Proteins genetics, Promoter Regions, Genetic genetics, Homeostasis, Gallbladder embryology, Gallbladder metabolism, SOXF Transcription Factors metabolism, SOXF Transcription Factors genetics, Bile Ducts, Extrahepatic metabolism, Bile Ducts, Extrahepatic embryology, Gene Expression Regulation, Developmental
- Abstract
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 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., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2025. Published by The Company of Biologists.)
- Published
- 2025
- Full Text
- View/download PDF