Fgf10 maintains notch activation, stimulates proliferation, and blocks differentiation of pancreatic epithelial cells
Fgf10 maintains notch activation, stimulates proliferation, and blocks differentiation of pancreatic epithelial cells
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DOI：
10.1002/dvdy.10368
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发表时间：
2003-10-01
影响因子：
2.5
通讯作者：
Edlund, H
中科院分区：
文献类型：
--
作者：
Hart, A;Papadopoulou, S;Edlund, H
胰腺是内胚层来源的器官，最初表现为原肠上皮的背侧和腹侧突起。存在于这些早期胰腺原基中的胰腺祖细胞增殖并最终产生所有胰腺细胞类型。成纤维细胞生长因子受体（FGFR）2b高亲和力配体FGF 10与胰腺上皮细胞增殖有关，并且我们先前已经表明Notch信号传导通过侧向抑制控制胰腺细胞分化。在发育中的胰腺中，激活的细胞内Notch似乎是维持细胞处于祖细胞状态所需的，部分是通过阻断促内分泌基因神经生成素3（ngn 3）的表达，从而阻断内分泌细胞分化。在这里，我们表明，FGF 10在转基因小鼠的胚胎胰腺中的持续表达也抑制胰腺细胞分化，同时刺激胰腺上皮细胞增殖。我们提供的证据表明，Fgf 10在发育中的胰腺中持续表达的影响之一是维持Notch激活，这导致胰腺上皮内ngn 3的表达受损。总之，我们的数据表明FGF 10/FGFR 2b信号传导在调节胰腺细胞增殖和分化中的作用，并且FGF 10/FGFR 2b信号传导影响Notch介导的侧向抑制途径。(C)2003 Wiley-Liss，Inc.
The pancreas is an endodermally derived organ that initially appears as a dorsal and ventral protrusion of the primitive gut epithelium. The pancreatic progenitor cells present in these early pancreatic anlagen proliferate and eventually give rise to all pancreatic cell types. The fibroblast growth factor receptor (FGFR) 2b high-affinity ligand FGF10 has been linked to pancreatic epithelial cell proliferation, and we have shown previously that Notch signalling controls pancreatic cell differentiation by means of lateral inhibition. In the developing pancreas, activated intracellular Notch appears to be required for maintaining cells in the progenitor state, in part by blocking the expression of the pro-endocrine gene neurogenin 3 (ngn3), and hence endocrine cell differentiation. Here, we show that persistent expression of Fgf10 in the embryonic pancreas of transgenic mice also inhibits pancreatic cell differentiation, while stimulating pancreatic epithelial cell proliferation. We provide evidence that one of the effects of the persistent expression of Fgf10 in the developing pancreas is maintained Notch activation, which results in impaired expression of ngn3 within the pancreatic epithelium. Together, our data suggest a role for FGF10/FGFR2b signalling in regulation of pancreatic cell proliferation and differentiation and that FGF10/FGFR2b signalling affects the Notch-mediated lateral inhibition pathway. (C) 2003 Wiley-Liss, Inc.