# Positive autoregulation of Sox17 is necessary for gallbladder and extrahepatic bile duct formation

## TL;DR

The study shows that the Sox17 gene's self-regulation is crucial for forming the gallbladder and bile ducts in mice.

## Contribution

The discovery of a SOX17-dependent autoregulatory loop controlling gallbladder and bile duct development is novel.

## Key findings

- A SOX17-binding cis-regulatory element in TSS2 is essential for gallbladder and bile duct formation.
- Reduced Sox17 expression disrupts the development of the biliary system in mice.
- Positive autoregulation of Sox17 maintains a critical threshold for proper organ development.

## 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.

Summary: A SOX17-binding cis-regulatory element in transcription start site 2 of Sox17 forms a positive autoregulatory feedback loop necessary for gallbladder and extra-hepatic bile duct formation.