Promoter elements in endocrine pancreas development and hormone regulation

Abstract:

The research upon the genetics of mammalian endocrine pancreas development gave rise to the detection of several genes that mediate decisions between different cell lineages that finally lead to four different hormone-producing cell types. Transcription factors such as Pdx1, Hnf6, ngn3, NeuroD/BETA2, Pax6 or Pax4 act within regulatory cascades and networks of transcriptional regulations that provide the genetic background for endocrine pancreas development. In adult animals the anatomical unit of the endocrine organ, the Islets of Langerhans, is built out of α, β, δ and PP cells producing the peptide hormones glucagaon, insulin, somatostatin and pancreatic polypeptide, respectively. Numerous promoter analyses of genes expressed in endocrine cells during development and adulthood have been performed. It turns out that the sequences of cis-regulatory elements within promoters of both, developmental control genes and peptide hormones, can show significant similarities. The relevance of such elements has been demonstrated by several deletion experiments and protein-DNA interaction assays. This review summarizes the currently known cis-regulatory elements that are important for islet development and provides the opportunity of detecting further pancreatic genes by discussing common promoter structures.