2 TRANSGENIC APPROACHES TO DEFINE THE CELL LINEAGES IN ENDOCRINE PANCREAS DEVELOPMENT

Ontogenic relationships between the different endocrine cell types of the islets of Langerhans were explored by generating transgenic mice, in which cells transcribing the glucagon, insulin, or pancreatic polyp eptide genes were destroyed through the promoter-targeted expression o f the diphtheria toxin A chain. In an alternate approach, to assess wh ether insulin cells are derived from precursors producing glucagon or PP, transgenic mice were generated bearing an insulin promoter-driven, and loxP-containing ('floxed') reporter transgene that can be irrever sibly 'tagged' by recombination. They were crossed with mice expressin g another transgene ('tagger') encoding Cre (cyclization recombination ) recombinase in either glucagon or PP cells. The results obtained usi ng both approaches indicate that neither glucagon nor insulin gene-exp ressing cells are the precursors to the other islet cells; also, they suggest that PP gene-expressing cells are necessary for the differenti ation of islet insulin and somatostatin cells, through a cell lineage or a paracrine relationship. (C) 1998 Elsevier Science Ireland Ltd. Al l rights reserved.