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

M Sander, L Sussel, J Conners, D Scheel… - …, 2000 - journals.biologists.com
M Sander, L Sussel, J Conners, D Scheel, J Kalamaras, FD Cruz, V Schwitzgebel
Development, 2000journals.biologists.com
Most insulin-producing β-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 β-cell precursors and blocks β-
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: β-cell precursors survive but fail to differentiate into β-cells throughout …
Abstract
Most insulin-producing β-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 β-cell precursors and blocks β-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: β-cell precursors survive but fail to differentiate into β-cells throughout development. Together, these experiments reveal two independently controlled pathways for β-cell differentiation, and place Nkx6.1 downstream of Nkx2.2 in the major pathway of β-cell differentiation.
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