Snail2, a mediator of epithelial-mesenchymal transitions, expressed in progenitor cells of the developing endocrine pancreas

Abstract

The mammalian pancreas develops by the expansion and morphogenesis of the epithelial cells of the foregut endoderm via the sequential activation of transcription factors that direct differentiation into the various pancreatic lineages. Implicit in this growth and differentiation are the temporal and spatial processes of cell migration and three-dimensional organization, which cooperate to form a properly functioning organ. In many organ systems, such as the kidney, heart, and neural crest derivatives, migration and tissue morphogenesis is accomplished by the transient conversion of stationary epithelial cells to migratory mesenchymal-like cells in a process known as epithelial-mesenchymal transition (EMT). We report the identification of the expression of the transcription factor Snail2/Slug, a known inducer of EMT and cell movement, in both the endocrine and exocrine cells of the developing mouse pancreas. Snail2 is expressed in Neurogenin3-positive endocrine progenitor cells, and expression is maintained during endocrine cell differentiation where it becomes increasingly restricted to the insulin-producing beta cells and somatostatin-producing delta cells. In the adult pancreas, the expression of Snail2 is maintained at low but detectable levels in all beta cells, indicating a latent role for Snail2 in the mature islet. These findings of Snail2 expression during endocrine pancreas development are relevant to the recent evidence demonstrating the involvement of EMT in the expansion of human islet tissue in vitro. EMT-like events appear to be involved in the development of the mammalian pancreas in vivo.