Essential roles of zebrafish bmp2a, fgf10 and fgf24 in the specification of the ventral pancreas

In vertebrates, pancreas and liver arise from bipotential progenitors located in the embryonic gut endoderm. BMP and FGF signalling pathways have been shown to induce hepatic specification while repressing pancreatic fate. Here, we show that BMP and FGF factors also play crucial function, at slightly later stages, in the specification of the ventral pancreas. By analyzing the pancreatic markers pdx1, ptf1a and hlxb9la in different zebrafish models of BMP loss-of-function, we demonstrate that the BMP pathway is required between 20-24 hpf to specify the ventral pancreatic bud. Knockdown experiments show that bmp2a, expressed in the lateral plate mesoderm at these stages, is essential for ventral pancreas specification. Bmp2a action is not restricted to the pancreatic domain and is also required for the proper expression of hepatic markers. By contrast, through the analysis of fgf10-/-; fgf24-/- embryos, we unveil the specific role of these two FGF ligands in the induction of the ventral pancreas and in the repression of the hepatic fate. These mutants display ventral pancreas agenesis and ectopic masses of hepatocytes. Overall, these data highlight the dynamic role of BMP and FGF in the patterning of the hepatopancreatic region.