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Homeobox gene Nkx6.1 lies downstream of Nkx2.2 in the major pathway of beta-cell formation in the pancreas.

http://www.ncbi.nlm.nih.gov/pubmed/11076772

Most insulin-producing beta-cells in the fetal mouse pancreas arise during the secondary transition, a wave of differentiation starting at embryonic day 13. Here, we show that disruption of homeobox gene Nkx6.1 in mice leads to loss of beta-cell precursors and blocks beta-cell neogenesis specifically during the secondary transition. In contrast, islet development in Nkx6. 1/Nkx2.2 double mutant embryos is identical to Nkx2.2 single mutant islet development: beta-cell precursors survive but fail to differentiate into beta-cells throughout development. Together, these experiments reveal two independently controlled pathways for beta-cell differentiation, and place Nkx6.1 downstream of Nkx2.2 in the major pathway of beta-cell differentiation.

Pubmed ID: 11076772 RIS Download

Mesh terms: Animals | Cell Differentiation | Gene Expression Regulation, Developmental | Genes, Homeobox | Homeodomain Proteins | Islets of Langerhans | Mice | Mice, Knockout | Mutation | Pancreas | Transcription Factors

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Associated grants

  • Agency: NIDDK NIH HHS, Id: DK21344
  • Agency: NIDDK NIH HHS, Id: DK41822
  • Agency: NINDS NIH HHS, Id: NS10184
  • Agency: NIDDK NIH HHS, Id: R01 DK021344

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