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PMID:20869363

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Citation

Kalousova, A, Mavropoulos, A, Adams, BA, Nekrep, N, Li, Z, Krauss, S, Stainier, DY and German, MS (2010) Dachshund homologues play a conserved role in islet cell development. Dev. Biol. 348:143-52

Abstract

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.

Links

PubMed PMC2997432 Online version:10.1016/j.ydbio.2010.09.007

Keywords

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

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DANRE:A0A2R8Q5U4

involved_in

GO:0031018: endocrine pancreas development

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-101217-1

P

Seeded From UniProt

complete

DANRE:A2AWB7

involved_in

GO:0031018: endocrine pancreas development

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-101217-1

P

Seeded From UniProt

complete

DANRE:B3DJL7

involved_in

GO:0031018: endocrine pancreas development

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-101217-1

P

Seeded From UniProt

complete

DANRE:F1QNJ8

involved_in

GO:0031018: endocrine pancreas development

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-101217-1

P

Seeded From UniProt

complete

DANRE:F1R4Z6

involved_in

GO:0031018: endocrine pancreas development

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-101217-1

P

Seeded From UniProt

complete

DANRE:Q1JPW0

involved_in

GO:0031018: endocrine pancreas development

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-101217-1

P

Seeded From UniProt

complete

DANRE:Q8QHJ2

involved_in

GO:0031018: endocrine pancreas development

ECO:0000315: mutant phenotype evidence used in manual assertion

ZFIN:ZDB-MRPHLNO-101217-1

P

Seeded From UniProt

complete

MOUSE:DACH1

acts_upstream_of_or_within

GO:0008283: cell population proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2448366

P

Seeded From UniProt

complete

MOUSE:DACH1

acts_upstream_of_or_within

GO:0000122: negative regulation of transcription by RNA polymerase II

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2448366

P

Seeded From UniProt

complete

MOUSE:DACH1

enables

GO:0000981: DNA-binding transcription factor activity, RNA polymerase II-specific

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:DACH1

acts_upstream_of_or_within

GO:0008283: cell population proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2448366

P

  • occurs_in:(EMAPA:18816)
  • acts_on_population_of:(CL:0000169)|occurs_in(EMAPA:18816)
  • acts_on_population_of:(CL:0000171)

Seeded From UniProt

complete


See also

References

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