Stabilization of beta-catenin impacts pancreas growth.
A recent study has shown that deletion of beta-catenin within the pancreatic epithelium results in a loss of pancreas mass. Here, we show that ectopic stabilization of beta-catenin within mouse pancreatic epithelium can have divergent effects on both organ formation and growth. Robust stabilization of beta-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 beta-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 beta-catenin signaling in the regulation of pancreas organ growth.
Heiser
Patrick W
PW
Diabetes Center, Department of Medicine, University of California, San Francisco, CA 94143, USA.
Lau
Janet
J
Taketo
Makoto M
MM
Herrera
Pedro L
PL
Hebrok
Matthias
M
D000818:Animals; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology; D051526:Fibroblast Growth Factor 10 / Q000502:physiology; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins / Q000502:physiology; D051379:Mice; D009929:Organ Size; D038081:Organogenesis; D010179:Pancreas / Q000166:cytology / Q000196:embryology* / Q000254:growth & development*; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism / Q000502:physiology; D051176:beta Catenin / Q000502:physiology*
C496464:Fgf10 protein, mouse; D051526:Fibroblast Growth Factor 10; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D015534:Trans-Activators; D051176:beta Catenin; C084010:pancreatic and duodenal homeobox 1 protein