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ZFIN ID: ZDB-PUB-101011-2
Dachshund homologues play a conserved role in islet cell development
Kalousova, A., Mavropoulos, A., Adams, B.A., Nekrep, N., Li, Z., Krauss, S., Stainier, D.Y., and German, M.S.
Date: 2010
Source: Developmental Biology   348(2): 143-152 (Journal)
Registered Authors: Krauss, Stefan, Mavropoulos, Anastasia, Stainier, Didier
Keywords: none
MeSH Terms:
  • Animals
  • Cell Differentiation
  • Cell Proliferation
  • Cyclin-Dependent Kinase Inhibitor p27/genetics
  • Cyclin-Dependent Kinase Inhibitor p27/metabolism
  • Embryo, Nonmammalian/metabolism
  • Eye Proteins/genetics
  • Eye Proteins/metabolism
  • Gene Expression Regulation, Developmental
  • Islets of Langerhans/cytology
  • Islets of Langerhans/embryology*
  • Islets of Langerhans/metabolism
  • Mice
  • Transcription Factors/physiology*
  • Zebrafish/embryology
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed: 20869363 Full text @ Dev. Biol.
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.