Notch/Rbp-j signaling prevents premature endocrine and ductal cell differentiation in the pancreas
Notch/Rbp-j signaling prevents premature endocrine and ductal cell differentiation in the pancreas
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DOI：
10.1016/j.cmet.2005.12.005
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发表时间：
2006-01-01
期刊：
影响因子：
29
通讯作者：
Nakao, K
中科院分区：
文献类型：
--
作者：
Fujikura, J;Hosoda, K;Nakao, K
为了研究Notch/Rbp-j信号传导在胰腺中的确切作用，我们通过将Rbp-j floxed小鼠与Pdx.cre或Rip.cre转基因小鼠杂交来灭活Rbp-j。在胰腺发育的初始阶段Rbp-j的丧失诱导了α和PP细胞分化的加速以及E11.5时神经生成素3（Ngn 3）阳性细胞数量的伴随减少。然后在E15，表达导管细胞标记物的细长管状结构是明显的;然而，腺泡和所有类型的内分泌细胞的分化减少。在胚胎后期，观察到代偿性腺泡细胞分化。由此产生的小鼠表现出胰岛素缺乏型糖尿病，伴有内分泌和外分泌胰腺发育不全。相比之下，β细胞中特异性Rbp-j的丢失并不影响β细胞的数量和功能。因此，我们的分析表明，Notch/Rbp-j信号传导防止胰腺祖细胞在胰腺早期发育期间过早分化为内分泌细胞和导管细胞。
To investigate the precise role of Notch/Rbp-j signaling in the pancreas, we inactivated Rbp-j by crossing Rbp-j floxed mice with Pdx.cre or Rip.cre transgenic mice. The loss of Rbp-j at the initial stage of pancreatic development induced accelerated alpha and PP cell differentiation and a concomitant decrease in the number of Neurogenin3 (Ngn3)-positive cells at E11.5. Then at E15, elongated tubular structures expressing ductal cell markers were evident; however, differentiation of acinar and all types of endocrine cells were reduced. During later embryonic stages, compensatory acinar cell differentiation was observed. The resultant mice exhibited insulin-deficient diabetes with both endocrine and exocrine pancreatic hypoplasia. In contrast, the loss of Rbp-j specifically in beta cells did not affect beta cell number and function. Thus, our analyses indicate that Notch/Rbp-j signaling prevents premature differentiation of pancreatic progenitor cells into endocrine and ductal cells during early development of the pancreas.