THE MORPHOGENESIS OF THE PANCREATIC MESENCHYME IS UNCOUPLED FROM THATOF THE PANCREATIC EPITHELIUM IN IPF1 PDX1-DEFICIENT MICE/

We have previously shown that mice carrying a null mutation in the hom eobox gene ipf1, now renamed to pdx1, selectively lack a pancreas, To elucidate the level at which PDX1 is required during the development o f the pancreas, we have in this study analyzed the early stages of pan creas ontogeny in PDX(-/-) mice. These analyses have revealed that the early inductive events leading to the formation of the pancreatic bud s and the appearance of the early insulin and glucagon cells occur in the PDX1-deficient embryos. However, the subsequent morphogenesis of t he pancreatic epithelium and the progression of differentiation of the endocrine cells are arrested in the pdx1(-/-) embryos. In contrast, t he pancreatic mesenchyme grows and develops, both morphologically and functionally, independently of the epithelium. We also show that the p ancreatic epithelium in the pdx1 mutants is unable to respond to the m esenchymal-derived signal(s) which normally promote pancreatic morphog enesis, Together these data provide evidence that PDX-1 acts cell auto nomously and that the lack of a pancreas in the pdx1(-/-) mice is due to a defect in the pancreatic epithelium.