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Publication : Dachshund homologues play a conserved role in islet cell development.

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.
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