Zebrafish sox9b is crucial for hepatopancreatic duct development and pancreatic endocrine cell regeneration

Recent zebrafish studies have shown that the late appearing pancreatic endocrine cells derive 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 Notchresponsive
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.