First Author | Kalousova A | Year | 2010 |
Journal | Dev Biol | Volume | 348 |
Issue | 2 | Pages | 143-52 |
PubMed ID | 20869363 | Mgi Jnum | J:166952 |
Mgi Id | MGI:4850233 | Doi | 10.1016/j.ydbio.2010.09.007 |
Citation | Kalousova A, et al. (2010) Dachshund homologues play a conserved role in islet cell development. Dev Biol 348(2):143-52 |
abstractText | All metazoans use insulin to control energy metabolism, but they secrete it from different cells: neurons in the central nervous system in invertebrates and endocrine cells in the gut or pancreas in vertebrates. Despite their origins in different germ layers, all of these insulin-producing cells share common functional features and gene expression patterns. In this study, we tested the role in insulin-producing cells of the vertebrate homologues of Dachshund, a transcriptional regulator that marks the earliest committed progenitors of the neural insulin-producing cells in Drosophila. Both zebrafish and mice expressed a single dominant Dachshund homologue in the pancreatic endocrine lineage, and in both species loss of this homologue reduced the numbers of all islet cell types including the insulin-producing beta-cells. In mice, Dach1 gene deletion left the pancreatic progenitor cells unaltered, but blocked the perinatal burst of proliferation of differentiated beta-cells that normally generates most of the beta-cell mass. In beta-cells, Dach1 bound to the promoter of the cell cycle inhibitor p27Kip1, which constrains beta-cell proliferation. Taken together, these data demonstrate a conserved role for Dachshund homologues in the production of insulin-producing cells. |