title: Zebrafish sox9b is crucial for hepatopancreatic duct development and pancreatic endocrine cell regeneration.
abstract: Recent zebrafish studies have shown that the late appearing pancreatic endocrine cells are derived from pancreatic ducts but the regulatory factors involved are still largely unknown. Here, we show that the zebrafish sox9b gene is expressed in pancreatic ducts where it labels the pancreatic Notch-responsive cells previously shown to be progenitors. Inactivation of sox9b disturbs duct formation and impairs regeneration of beta cells from these ducts in larvae. sox9b expression in the midtrunk endoderm appears at the junction of the hepatic and ventral pancreatic buds and, by the end of embryogenesis, labels the hepatopancreatic ductal system as well as the intrapancreatic and intrahepatic ducts. Ductal morphogenesis and differentiation are specifically disrupted in sox9b mutants, with the dysmorphic hepatopancreatic ducts containing misdifferentiated hepatocyte-like and pancreatic-like cells. We also show that maintenance of sox9b expression in the extrapancreatic and intrapancreatic ducts requires FGF and Notch activity, respectively, both pathways known to prevent excessive endocrine differentiation in these ducts. Furthermore, beta cell recovery after specific ablation is severely compromised in sox9b mutant larvae. Our data position sox9b as a key player in the generation of secondary endocrine cells deriving from pancreatic ducts in zebrafish.
authors.affiliation: Unit of Molecular Biology and Genetic Engineering, Giga-Research, University of Liège, 1 avenue de l'Hôpital B34, B-4000 Sart-Tilman, Belgium. Isabelle.manfroid@ulg.ac.be
authors.forename: Isabelle
authors.initials: I
authors.lastname: Manfroid
authors.forename: Aurélie
authors.initials: A
authors.lastname: Ghaye
authors.forename: François
authors.initials: F
authors.lastname: Naye
authors.forename: Nathalie
authors.initials: N
authors.lastname: Detry
authors.forename: Sarah
authors.initials: S
authors.lastname: Palm
authors.forename: Luyuan
authors.initials: L
authors.lastname: Pan
authors.forename: Taylur P
authors.initials: TP
authors.lastname: Ma
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: Meritxell
authors.initials: M
authors.lastname: Rovira
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Martial
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Parsons
authors.forename: Cecilia B
authors.initials: CB
authors.lastname: Moens
authors.forename: Marianne L
authors.initials: ML
authors.lastname: Voz
authors.forename: Bernard
authors.initials: B
authors.lastname: Peers
mesh_terms: D000818:Animals; D005346:Fibroblast Growth Factors / Q000502:physiology; D043143:Hepatopancreas / Q000196:embryology* / Q000502:physiology; D007515:Islets of Langerhans / Q000502:physiology*; D010179:Pancreas / Q000166:cytology / Q000502:physiology; D051880:Receptors, Notch / Q000502:physiology; D012038:Regeneration; D055758:SOX9 Transcription Factor / Q000502:physiology*; D015398:Signal Transduction; D015027:Zebrafish / Q000196:embryology* / Q000502:physiology; D029961:Zebrafish Proteins / Q000502:physiology*
chemical_list: D051880:Receptors, Notch; D055758:SOX9 Transcription Factor; C504919:Sox9b protein, zebrafish; D029961:Zebrafish Proteins; D005346:Fibroblast Growth Factors