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

Development. 2000 Dec;127(24):5533-40.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Differentiation
  • Gene Expression Regulation, Developmental
  • Genes, Homeobox*
  • Homeodomain Proteins / genetics*
  • Islets of Langerhans / cytology
  • Islets of Langerhans / embryology*
  • Islets of Langerhans / metabolism*
  • Mice
  • Mice, Knockout
  • Mutation
  • Pancreas / cytology
  • Pancreas / embryology
  • Pancreas / metabolism
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Zebrafish Proteins

Substances

  • Homeodomain Proteins
  • Nkx2.2 protein
  • Nkx6-1 protein, mouse
  • Transcription Factors
  • Zebrafish Proteins