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FGF10 regulates hepatopancreatic ductal system differentiation
Author(s) -
Si Dong P. D.,
Munson Chantilly A.,
Norton William H. J.,
Neumann Carl J.,
Stainier Didier Y. R.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a876-b
Subject(s) - mesenchyme , biology , ductal cells , endoderm , fgf10 , pancreas , pdx1 , mesoderm , homeobox , microbiology and biotechnology , mesenchymal stem cell , embryonic stem cell , anatomy , medicine , endocrinology , fibroblast growth factor , gene expression , receptor , gene , genetics , transcription factor
The hepatopancreatic ductal system, which consists of the common bile, cystic, extra hepatic and extra pancreatic ducts, joins the liver, pancreas, and gallbladder together into the intestine through the hepatopancreatic ampulla. Differentiation of the hepatopancreatic ductal system occurs concurrently with liver and pancreas differentiation. However unlike the liver and pancreas, the genetic mechanisms regulating hepatopancreatic ductal system development is largely unknown. Here, we show that mesenchymal cells, marked by the expression of the LIM homeodomain protein, ISL1, surround the developing hepatopancreatic ductal system and intestine but are absent around the pancreas and liver. Therefore, we hypothesized that these surrounding ISL1+ mesenchymal cells may be signaling to the presumptive hepatopancreatic duct to regulate its development. We show that the genes encoding FGF10 ligand and its high affinity receptor, FGFR2, are expressed in the mesenchyme and endoderm, respectively. In fgf10 null embryos, expression of the fgf target gene, dusp6, is lost from the organ‐forming region of the endoderm, suggesting that the endoderm receives fgf10 signaling from the mesenchyme. We also find that the hepatopancreatic ductal epithelium of fgf10 null embryos is dysmorphic and expanded. Gene expression analyses of fgf10 null embryos indicate that the hepatopancreatic ductal system and adjacent intestinal cells mis‐differentiate into hepatic cells and pancreatic endocrine and exocrine cells. Our findings demonstrate that cells of the presumptive hepatopancreatic ductal system and adjacent intestine are multipotent and poised to become pancreatic and hepatic tissues in absence of fgf10 signaling from the mesenchyme.