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First published online 12 April 2006
doi: 10.1242/dev.02366
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1 Diabetes Center, Department of Medicine, University of California, San
Francisco, CA 94143, USA.
2 Department of Pharmacology, Graduate School of Medicine, Kyoto University,
Kyoto, 606-8501, Japan.
3 Department of Genetic Medicine and Development, University of Geneva Medical
School, Geneva CH-1211, Switzerland.
* Author for correspondence (e-mail: mhebrok{at}diabetes.ucsf.edu)
Accepted 16 March 2006
A recent study has shown that deletion of ß-catenin within the pancreatic epithelium results in a loss of pancreas mass. Here, we show that ectopic stabilization of ß-catenin within mouse pancreatic epithelium can have divergent effects on both organ formation and growth. Robust stabilization of ß-catenin during early organogenesis drives changes in hedgehog and Fgf10 signaling and induces a loss of Pdx1 expression in early pancreatic progenitor cells. Together, these perturbations in early pancreatic specification culminate in a severe reduction of pancreas mass and postnatal lethality. By contrast, inducing the stabilized form of ß-catenin at a later time point in pancreas development causes enhanced proliferation that results in a dramatic increase in pancreas organ size. Taken together, these data suggest a previously unappreciated temporal/spatial role for ß-catenin signaling in the regulation of pancreas organ growth.
Key words: ß-Catenin, FGF, Hedgehog, Organ size, Pancreas development, Pdx1, Wnt, Mouse, Pancreatomegaly
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