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Dachshund homologues play a conserved role in islet cell development.

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 β-cells. In mice, Dach1 gene deletion left the pancreatic progenitor cells unaltered, but blocked the perinatal burst of proliferation of differentiated β-cells that normally generates most of the β-cell mass. In β-cells, Dach1 bound to the promoter of the cell cycle inhibitor p27Kip1, which constrains β-cell proliferation. Taken together, these data demonstrate a conserved role for Dachshund homologues in the production of insulin-producing cells.

Pubmed ID: 20869363

Authors

  • Kalousova A
  • Mavropoulos A
  • Adams BA
  • Nekrep N
  • Li Z
  • Krauss S
  • Stainier DY
  • German MS

Journal

Developmental biology

Publication Data

December 15, 2010

Associated Grants

  • Agency: NIDDK NIH HHS, Id: P30 DK063720
  • Agency: NIDDK NIH HHS, Id: P30 DK063720
  • Agency: NIDDK NIH HHS, Id: P30 DK063720-02
  • Agency: NIDDK NIH HHS, Id: P30 DK063720-03
  • Agency: NIDDK NIH HHS, Id: P30 DK063720-04
  • Agency: NIDDK NIH HHS, Id: P30 DK063720-05
  • Agency: NIDDK NIH HHS, Id: P30 DK063720-06A1
  • Agency: NIDDK NIH HHS, Id: P30 DK063720-07
  • Agency: NIDDK NIH HHS, Id: R01 DK021344
  • Agency: NIDDK NIH HHS, Id: R01 DK021344-25
  • Agency: NIDDK NIH HHS, Id: R01 DK021344-26
  • Agency: NIDDK NIH HHS, Id: R01 DK021344-27A2
  • Agency: NIDDK NIH HHS, Id: R01 DK021344-28
  • Agency: NIDDK NIH HHS, Id: R01DK075032
  • Agency: NIDDK NIH HHS, Id: R01DK21344
  • Agency: NIDDK NIH HHS, Id: U19 DK061245
  • Agency: NIDDK NIH HHS, Id: U19 DK061245-04
  • Agency: NIDDK NIH HHS, Id: U19 DK61245

Mesh Terms

  • Animals
  • Cell Differentiation
  • Cell Proliferation
  • Cyclin-Dependent Kinase Inhibitor p27
  • Embryo, Nonmammalian
  • Eye Proteins
  • Gene Expression Regulation, Developmental
  • Islets of Langerhans
  • Mice
  • Transcription Factors
  • Zebrafish
  • Zebrafish Proteins