Factors regulating the genesis and maintenance of pancreatic beta cell mass

Over the past several years, a network of transcription factors has been identified that are required to generate the different pancreatic cell lineages. Our laboratory is studying two transcription factors expressed in the developing pancreas, pdx1 and Foxm1. pdx1 is expressed broadly in the pancreatic bud epithelium early in development, and becomes enriched in insulin‐producing β cells by birth. Conditional gene inactivation reveals that pdx1 function is required for the generation and maintenance of mature pancreatic endocrine cells. Conversely, the cell cycle transcriptional regulator Foxm1 is most highly expressed in embryonic endocrince cells, with very few expressing cells observed in adult islets. Using conditional gene inactivation, we found that embryonic deletion of Foxm1 does not effect islet neogenesis, but rather results in a gradual loss of β cell mass after birth. Thus, the mechanisms used for expansion of endocrine mass postnatally may differ from pathways used during embryogenesis. Factors responsible for maintenance and growth of β cell mass might be targets for regeneration in vivo or expandsion of β cells ex vivo from adult sources.