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Updated: May 13, 2026

Surgical Injury to the Mouse Pancreas through Ligation of the Pancreatic Duct as a Model for Endocrine and Exocrine Reprogramming and Proliferation
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Sox9b is a key regulator of pancreaticobiliary ductal system development

Marion Delous1, Chunyue Yin, Donghun Shin

  • 1Department of Biochemistry, Program in Developmental and Stem Cell Biology, Liver Center and Diabetes Center, University of California San Francisco, San Francisco, California, United States of America. marion.delous@ucsf.edu

Plos Genetics
|June 22, 2012
PubMed

Insights

SOX9 is crucial for developing the pancreaticobiliary ductal system. Zebrafish studies reveal SOX9B mutations cause severe duct malformations and cholestasis, highlighting SOX9

Area of Science:

  • Developmental biology
  • Zebrafish models
  • Molecular genetics

Background:

  • The pancreaticobiliary ductal system's development is poorly understood.
  • SOX9 is expressed in this system, but mouse models have limitations for functional studies.
  • Zebrafish offer a viable model for SOX9 function in duct development.

Purpose of the Study:

  • To investigate the role of SOX9 in pancreaticobiliary ductal system morphogenesis using zebrafish.
  • To analyze the consequences of SOX9B loss-of-function on duct development and identify potential signaling interactions.

Main Methods:

  • Utilized a zebrafish nonsense allele of sox9b (sox9b(fh313)) for loss-of-function analysis.
  • Examined embryonic and larval stages for ductal system morphology and cell differentiation.
  • Investigated the interaction between Sox9b and Notch signaling pathways.

Main Results:

  • sox9b(fh313) mutants exhibit severe pancreaticobiliary duct malformations, including cholestasis, ductal proliferation, cysts, and fibrosis.
  • Hepatopancreatic ductal cells mis-differentiate, and intrahepatic and intrapancreatic duct formation is impaired.
  • Sox9b functions with Notch signaling to regulate intrahepatic biliary network formation.

Conclusions:

  • SOX9 plays a critical role in the morphogenesis of the pancreaticobiliary ductal system.
  • SOX9B is essential for proper ductal cell differentiation and network assembly.
  • Human SOX9 is a candidate gene for pancreaticobiliary duct malformation disorders.

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