Distribution and function of the adhesion molecule BEN during rat development.

It is well established that the notochord influences the development of adjacent neural and mesodermal tissue. Involvement of the notochord in the differentiation of the dorsal pancreas has been demonstrated. However, our knowledge of the signals involved in pancreatic development is still incomplete. In order to identify proteins potentially implicated during pancreatic differentiation, we raised and characterized monoclonal antibodies against previously established embryonic pancreatic ductal epithelial cell lines (BUD and RED). Using the MAb 2117, the cell surface antigen 2117 (Ag 2117) was cloned. The predicted sequence for Ag 2117 is the rat homologue of BEN. Initially reported as a protein expressed on epithelial cells of the chicken bursa of Fabricius, BEN is expressed in a variety of tissues during development and described as a marker for the developing central and peripheral chicken nervous systems. A role has been suggested for BEN in the adhesion of stem cells and progenitor cells to the blood-forming tissue microenvironment. In this study, we demonstrate that BEN, initially expressed exclusively in the notochord during the early development of rat, is implicated in pancreatic development. We show that Ag 2117 regulates the pancreatic epithelial cell growth through the ras and Jun kinase pathways. In addition, we demonstrate that Ag 2117 is able to regulate the expression of the transcription factor PDX1, required for insulin gene expression, in embryonic pancreas organ cultures. Copyright 1999 Academic Press.