Identification of FGF10 targets in the embryonic lung epithelium during bud morphogenesis
Identification of FGF10 targets in the embryonic lung epithelium during bud morphogenesis
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DOI：
10.1074/jbc.m410714200
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发表时间：
2005-02-11
影响因子：
4.8
通讯作者：
Cardoso, WV
中科院分区：
文献类型：
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作者：
Lü, JN;Izvolsky, KI;Cardoso, WV
遗传学研究表明Fgf10-Fgfr2信号是胚胎芽形态发生的关键调控因子。然而，对于Fgf10在这一过程中的转录靶点知之甚少。在这里，我们发现在缺乏其他生长因子和间质的情况下，肺上皮外植体在fgf10介导的出芽过程中基因表达的全局变化。靶标定位于胚胎肺中内源性Fgf10信号活跃的部位，并通过Fgf10蛋白局部应用在完整肺中的诱导证实。我们发现，出芽初期的特征是与细胞重排、细胞迁移、炎症过程和脂质代谢相关的基因显著上调，而不是细胞增殖。我们还发现，一些与肿瘤侵袭和转移行为有关的基因是肺和其他发育器官中Fgf10的上皮靶点，这些靶点依赖于Fgf10- fgfr2信号传导来正确形成。我们的方法确定了多种生物过程中常见的Fgf10靶点，并提供了Fgf信号调节上皮细胞行为的潜在机制的见解。
Genetic studies implicate Fgf10-Fgfr2 signaling as a critical regulator of bud morphogenesis in the embryo. However, little is known about the transcriptional targets of Fgf10 during this process. Here we identified global changes in gene expression in lung epithelial explants undergoing FGF10-mediated budding in the absence of other growth factors and mesenchyme. Targets were confirmed by their localization at sites where endogenous Fgf10 signaling is active in embryonic lungs and by demonstrating their induction in intact lungs in response to local application of FGF10 protein. We show that the initial stages of budding are characterized by marked up-regulation of genes associated with cell rearrangement and cell migration, inflammatory process, and lipid metabolism but not cell proliferation. We also found that some genes implicated in tumor invasion and metastatic behavior are epithelial targets of Fgf10 in the lung and other developing organs that depend on Fgf10-Fgfr2 signaling to properly form. Our approach identifies Fgf10 targets that are common to multiple biological processes and provides insights into potential mechanisms by which Fgf signaling regulates epithelial cell behavior.