FGF10 signaling maintains the pancreatic progenitor cell state revealing a novel role of Notch in organ development
FGF10 signaling maintains the pancreatic progenitor cell state revealing a novel role of Notch in organ development
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DOI：
10.1016/j.ydbio.2003.08.013
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发表时间：
2003-12-15
影响因子：
2.7
通讯作者：
Jensen, J
中科院分区：
文献类型：
--
作者：
Norgaard, GA;Jensen, JN;Jensen, J
FGF 10通过控制间充质-上皮信号传导在几种组织的形态发生中起重要作用。在胰腺中，需要间充质FGF 10来维持表达Pdx 1的上皮祖细胞群，并且在不存在FGF 10信号传导的情况下。这些细胞不能增殖。FGF 10在胰腺上皮中的异位表达引起胰腺祖细胞增殖增加和所有细胞类型的胰腺细胞分化的废除。一个增生的胰腺组成的未分化的细胞表达Pdx 1，Nkx6.1，和细胞粘附标志物通常表征早期胰腺祖细胞的结果。即使在妊娠晚期胰腺细胞的增殖减慢，分化也减弱，这表明FGF 10的营养作用与其对细胞分化的影响无关。FGF 10阳性胰腺细胞表达Notch 1和Notch 2、Notch配体基因Jagged 1和Jagged 2以及Notch靶基因Hes 1。Notch的这种激活不同于先前认识到的侧抑制机制。这些数据表明，FGF 10信号传导在Notch激活水平上整合细胞生长和终末分化，揭示了胰腺发育过程中这种关键信号传导系统的第二种新作用。(C)2003年爱思唯尔公司All rights reserved.
FGF10 plays an important role in the morphogenesis of several tissues by control of mesenchymal-to-epithelial signaling. In the pancreas, mesenchymal FGF10 is required to maintain the Pdx1-expressing epithelial progenitor cell population, and in the absence of FGF10 signaling. these cells fail to proliferate. Ectopic expression of FGF10 in the pancreatic epithelium caused increased proliferation of pancreatic progenitor cells and abrogation of pancreatic cell differentiation of all cell types. A hyperplastic pancreas consisting of undifferentiated cells expressing Pdx1, Nkx6.1, and cell adhesion markers normally characterizing early pancreatic progenitor cells resulted. Differentiation was attenuated even as proliferation of the pancreatic cells slowed during late gestation, suggesting that the trophic effect of FGF10 was independent of its effects upon cell differentiation. The FGF10-positive pancreatic cells expressed Notch1 and Notch2, the Notch-ligand genes Jagged1 and Jagged2, as well as the Notch target gene Hes1. This activation of Notch is distinct from the previously recognized mechanism of lateral inhibition. These data suggest that FGF10 signaling serves to integrate cell growth and terminal differentiation at the level of Notch activation, revealing a novel second role of this key signaling system during pancreatic development. (C) 2003 Elsevier Inc. All rights reserved.