Heiser Patrick W, Lau Janet, Taketo Makoto M, Herrera Pedro L, Hebrok Matthias
Diabetes Center, Department of Medicine, University of California, San Francisco, CA 94143, USA.
Development. 2006 May;133(10):2023-32. doi: 10.1242/dev.02366. Epub 2006 Apr 12.
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.
最近的一项研究表明，胰腺上皮细胞中β-连环蛋白的缺失会导致胰腺质量的丧失。在此，我们表明，小鼠胰腺上皮细胞中β-连环蛋白的异位稳定对器官形成和生长可能产生不同的影响。在早期器官发生过程中β-连环蛋白的强烈稳定会驱动刺猬信号通路和Fgf10信号的变化，并诱导早期胰腺祖细胞中Pdx1表达的丧失。这些早期胰腺特化的扰动共同导致胰腺质量的严重减少和出生后死亡。相比之下，在胰腺发育的后期时间点诱导β-连环蛋白的稳定形式会导致增殖增强，从而导致胰腺器官大小急剧增加。综上所述，这些数据表明β-连环蛋白信号在胰腺器官生长调节中具有以前未被认识到的时空作用。
