Regulation of gene expression in the embryonic pancreas by Oc1 and its impact on postnatal function

Abstract

The pancreas is a dual function organ contributing to both blood glucose homeostasis and digestion. These functions are carried out by the endocrine and exocrine compartments of the pancreas, respectively, which derive from common multipotent progenitor cells (MPCs) during embryonic development. The differentiation process for the cells composing both the endocrine and exocrine compartments is highly orchestrated by regulatory transcription factors. Previous work from our lab showed that one such factor, Onecut 1 (Oc1), is essential for initiating endocrine development, proper duct development, and appears necessary for acinar cell development. Using gene expression and physiologic analyses of genetically altered mouse models we have determined that threshold-dependent cooperation between Oc1 and another transcription factor, Pancreatic and duodenal homeobox 1 (Pdx1) in MPCs is necessary for proper endocrine specification, differentiation, maturation, and function. Additionally, we have concluded that Oc1 is not necessary in differentiated acinar cells, however, we have identified novel targets of Oc1 in exocrine pancreas development.