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Development, Vol 127, Issue 24 5533-5540, Copyright © 2000 by Company of Biologists

JOURNAL ARTICLES

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

M Sander, L Sussel, J Conners, D Scheel, J Kalamaras, F Dela Cruz, V Schwitzgebel, A Hayes-Jordan and M German
Hormone Research Institute, University of California San Francisco, San Francisco, CA 94143-0534, USA.

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.


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