EXPRESSION OF MURINE STF-1, A PUTATIVE INSULIN GENE-TRANSCRIPTION FACTOR, IN BETA-CELLS OF PANCREAS, DUODENAL EPITHELIUM AND PANCREATIC EXOCRINE AND ENDOCRINE PROGENITORS DURING ONTOGENY

The X1Hbox 8 homeodomain protein of Xenopus and STF-1, its mammalian h omolog, are selectively expressed by beta cells of adult mouse pancrea tic islets, where they are likely to regulate insulin expression, We s ought to determine whether the expression of the homeobox protein/s du ring mouse embryonic development was specific to beta cells or, altern atively, whether X1Hbox 8/STF-1 protein/s were initially expressed by multipotential precursors and only later became restricted to the insu lin-containing cells. With two antibodies, we studied the localization of STF-1 during murine pancreatic development. In embryos, as in adul ts, STF-1 was expressed by most beta cells, by subsets of the other is let cell types and by mucosal epithelial cells of the duodenum. In add ition, most epithelial tells of the pancreatic duct and exocrine cells of the pancreas transiently contained STF-1. We conclude that in mous e, STF-1 not only Labels a domain of intestinal epithelial cells but a lso provides a spatial and temporal marker of endodermal commitment to a pancreatic and subsequently, to an endocrine beta cell fate. We pro pose a model of pancreatic cell development that suggests that exocrin e and endocrine (alpha, beta, partial derivative and PP) cells arise f rom a common precursor pool of STF-1(+) cells and that progression tow ards a defined monospecific non-beta cell type is correlated with loss of STF-1 expression.