Fibroblast growth factor 10 (FGF10) and branching morphogenesis in the embryonic mouse lung.
Fibroblast growth factor 10 (FGF10) and branching morphogenesis in the embryonic mouse lung.
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发表时间：
1997-12
期刊：
影响因子：
4.6
通讯作者：
S. Bellusci;J. Grindley;H. Emoto;N. Itoh;B. Hogan
中科院分区：
文献类型：
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作者：
S. Bellusci;J. Grindley;H. Emoto;N. Itoh;B. Hogan
在小鼠肺形态发生过程中，远端间充质调节邻近内胚层的生长和分支。我们在此报道成纤维细胞生长因子10 （Fgf10）在肺发育早期的远端芽附近的间质中动态表达。基因表达的时空格局表明，Fgf10在定向生长中起作用，并可能诱导上皮芽的形成，Fgf10的正、负调节因子均由内胚层产生。在内胚层过表达Shh的转基因肺中，Fgf10转录减少，表明高水平的Shh下调了Fgf10。将FGF10添加到基质或胶原凝胶培养的胚胎11.5天的肺组织（内胚层加间质）中，24小时后内胚层出现囊状扩张。在基质凝胶中，而不是胶原蛋白中，在48-60小时后会出现大量的出芽。这种反应包括内胚层细胞增殖速率的增加。FGF1、FGF7和FGF10的活性也直接在体外培养的离体内胚层上进行了检测。在这些条件下，FGF1立即诱导内胚层萌发，而FGF7和FGF10最初诱导内胚层的扩张。然而，在24小时内，FGF10处理的样品产生了多个芽，而fgf7处理的内胚层在所有浓度的因子测试中都没有进展到芽的形成。尽管外源性FGF1、FGF7和FGF10在体外具有重叠的活性，但它们在体内的表达模式与早期分支事件有很大的不同。我们得出结论，在肺发育早期，中胚层中FGF10的局部来源调节内胚层的增殖和芽的生长。
During mouse lung morphogenesis, the distal mesenchyme regulates the growth and branching of adjacent endoderm. We report here that fibroblast growth factor 10 (Fgf10) is expressed dynamically in the mesenchyme adjacent to the distal buds from the earliest stages of lung development. The temporal and spatial pattern of gene expression suggests that Fgf10 plays a role in directional outgrowth and possibly induction of epithelial buds, and that positive and negative regulators of Fgf10 are produced by the endoderm. In transgenic lungs overexpressing Shh in the endoderm, Fgf10 transcription is reduced, suggesting that high levels of SHH downregulate Fgf10. Addition of FGF10 to embryonic day 11.5 lung tissue (endoderm plus mesenchyme) in Matrigel or collagen gel culture elicits a cyst-like expansion of the endoderm after 24 hours. In Matrigel, but not collagen, this is followed by extensive budding after 48-60 hours. This response involves an increase in the rate of endodermal cell proliferation. The activity of FGF1, FGF7 and FGF10 was also tested directly on isolated endoderm in Matrigel culture. Under these conditions, FGF1 elicits immediate endodermal budding, while FGF7 and FGF10 initially induce expansion of the endoderm. However, within 24 hours, samples treated with FGF10 give rise to multiple buds, while FGF7-treated endoderm never progresses to bud formation, at all concentrations of factor tested. Although exogenous FGF1, FGF7 and FGF10 have overlapping activities in vitro, their in vivo expression patterns are quite distinct in relation to early branching events. We conclude that, during early lung development, localized sources of FGF10 in the mesoderm regulate endoderm proliferation and bud outgrowth.