FGF-10 is a chemotactic factor for distal epithelial buds during lung development

FGF-10 is a chemotactic factor for distal epithelial buds during lung development
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DOI:
10.1006/dbio.1998.8994
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发表时间:
1998-09-15
影响因子:
2.7
通讯作者:
Cardoso, WV
Cardoso, WV
中科院分区:
生物学3区
文献类型:
--
作者:
Park, WY;Miranda, B;Cardoso, WV

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成纤维细胞生长因子(FGF)信号传导是几个物种的呼吸系统中的正常上皮分支所需的。最近的研究表明,FGF-10可能是肺分支形态发生的关键调节因子,基于其在早期肺中的表达模式及其在体外诱导上皮出芽的能力。在这项研究中,我们调查是否FGF-10能够直接肺上皮芽发育过程中的适当位置。我们使用FGF-10浸泡的肝素珠在培养的肺中维持局部高水平的FGF-10。FGF-10对远端而不是近端肺上皮发挥强大的趋化作用。上皮芽在24小时内向FGF-10源生长,随后在珠周围形成同心上皮层。BrdU掺入分析表明,FGF-10,与FGF-7相反,是一个温和的肺上皮细胞增殖因子。在缺乏间充质的情况下,FGF-10需要相关的增殖信号来诱导芽迁移。这可以通过来自肺间充质的提取物或FGF-7(也存在于早期胚胎肺中的生长因子)来提供。FGF-10似乎不干扰早期上皮细胞分化。FGF-10在肺上皮中的化学引诱作用使人想起果蝇FGF直系同源物在发育中的气管上皮中无分支的图案化作用,这表明这些基因的功能在进化过程中是保守的。(C)北京:科学出版社.
Fibroblast growth factor (FGF) signaling is required for normal epithelial branching in the respiratory system of several species. Recent studies have shown that FGF-10 may be a key regulator of lung branching morphogenesis, based on its pattern of expression in the early lung and its ability to induce epithelial budding in vitro. In this study we investigate whether FGF-10 is able to direct lung epithelial buds to proper positions during development. We maintained localized high levels of FGF-10 in cultured lungs using FGF-10-soaked heparin beads. FGF-10 exerts a powerful chemoattractant effect on the distal but not on proximal lung epithelium. Epithelial buds grow toward an FGF-10 source within 24 h, and subsequently form concentric layers of epithelium around the bead. BrdU incorporation analysis suggests that FGF-10, in contrast to FGF-7, is a modest proliferation factor for the lung epithelium. In the absence of mesenchyme FGF-10 requires an associated proliferative signal to induce bud migration. This can be provided by extract from lung mesenchyme, or by FGF-7, a growth factor also present in the early embryonic lung. FGF-10 does not seem to interfere with early epithelial cell differentiation. The chemoattractant effect of FGF-10 in the lung epithelium is reminiscent of the patterning effect of the Drosophila FGF ortholog branchless in the developing tracheal epithelium, suggesting that the function of these genes has been conserved during evolution. (C) 1998 Academic Press.