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

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