Rbp-j regulates expansion of pancreatic epithelial cells and their differentiation into exocrine cells during mouse development
Rbp-j regulates expansion of pancreatic epithelial cells and their differentiation into exocrine cells during mouse development
复制标题
DOI：
10.1002/dvdy.21310
复制
发表时间：
2007-10-01
影响因子：
2.5
通讯作者：
Nakao, Kazuwa
中科院分区：
文献类型：
--
作者：
Fujikura, Junji;Hosoda, Kiminori;Nakao, Kazuwa
Notch信号传导调节各种组织中的细胞命运决定。我们已经报道了使用Pdx.cre小鼠产生具有胰腺特异性敲除Rbp-j的小鼠。这些小鼠表现出过早的内分泌和导管分化。我们现在使用Ptt1a.cre小鼠产生了Rbp-j基因在Ptf 1a表达细胞中失活的小鼠。Rbp-j（f1 f）Ptf1a.cre小鼠中Cre介导的缺失的时间比Rbp-j（f1 f）Pdx.cre小鼠晚1天。在Rbp-j（f1 f）Ptf1a.cre小鼠胰腺中，在E13.5，Hes 1表达减少。伴随着上皮生长减少，但过早的内分泌细胞分化是最小的。在E15.5，Pdx 1表达被抑制，腺泡细胞分化减少，但在围产期观察到腺泡细胞增殖增加。我们的研究表明，除了其在防止早期内分泌细胞过早分化的作用，Rbp-j调节上皮细胞的生长，Pdx 1的表达，和腺泡细胞分化在胰腺中期的发展。
Notch signaling regulates cell fate determination in various tissues. We have reported the generation of mice with a pancreas-specific knockout of Rbp-j using Pdx.cre mice. Those mice exhibited premature endocrine and ductal differentiation. We now generated mice in which the Rbp-j gene was inactivated in Ptf1a-expressing cells using Ptt1a.cre mice. The timing of the Cre-mediated deletion in Rbp-j(f1f) Ptf1a.cre mice is 1 day later than that in Rbp-j(f1f) Pdx.cre mice. In Rbp-j(f1f)Ptf1a.cre mouse pancreases, at E13.5, the reduced Hes1 expression. was accompanied by reduced epithelial growth, but premature endocrine cell differentiation was minimal. At E15.5, Pdx1 expression was repressed and acinar cell differentiation was reduced, but an increase in acinar cell proliferation was observed during the perinatal period. Our study indicates that, in addition to its role in preventing premature differentiation of early endocrine cells, Rbp-j regulates epithelial growth, Pdx1 expression, and acinar cell differentiation during mid-pancreatic development.