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

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


  • Sander M
  • Sussel L
  • Conners J
  • Scheel D
  • Kalamaras J
  • Dela Cruz F
  • Schwitzgebel V
  • Hayes-Jordan A
  • German M


Development (Cambridge, England)

Publication Data

December 2, 2000

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

Mesh Terms

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