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

作者：Maike Sander, Lori Sussel, Jennifer R. Conners, David Scheel, Julie Kalamaras, Filemon S. Dela Cruz, Valérie Schwitzgebel, Andrea Anita Hayes-Jordan, Michael S. German · 发表于：Development · 年份：2000 · DOI：10.1242/dev.127.24.5533 · 被引用次数：526 · 研究领域：Pancreatic function and diabetes、Diabetes and associated disorders、Diabetes Management and Research

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.