Disruption of Fgf10/Fgfr2b-coordinated epithelial-mesenchymal interactions causes cleft palate
Disruption of Fgf10/Fgfr2b-coordinated epithelial-mesenchymal interactions causes cleft palate
复制标题
DOI：
10.1172/jci200420384
复制
发表时间：
2004-06-01
影响因子：
15.9
通讯作者：
Rice, DPC
中科院分区：
文献类型：
--
作者：
Rice, R;Spencer-Dene, B;Rice, DPC
经典的研究表明，早期腭形成发展通过上皮间质的相互作用，在这项研究中，我们揭示了哪些信号控制这一过程。使用Fgf 10（-/-）、FGF受体2b（-/-）（Fgfr 2b（-/-））和Sonic hedgehog（Shh）突变小鼠，它们都表现出腭裂，我们表明Shh是Fgf 10/Fgfr 2b信号传导的下游靶点。我们的研究结果表明，间充质FGF 10调节上皮表达的Shh，这反过来又信号回间充质。这通过证明不仅在Fgfr 2b（-/-）小鼠的腭上皮中而且在间充质中的细胞增殖减少来证实。这些结果揭示了一个新的作用，成纤维细胞生长因子信号在哺乳动物腭发育。我们发现，协调上皮间质相互作用是必不可少的腭发育的初始阶段，需要一个FGF-Shh信号网络。
Classical research has suggested that early palate formation develops via epithelial-mesenchymal interactions, and in this study we reveal which signals control this process. Using Fgf10(-/-), FGF receptor 2b(-/-)(Fgfr2b(-/-)), and Sonic hedgehog (Shh) mutant mice, which all exhibit cleft palate, we show that Shh is a down-stream target of Fgf10/Fgfr2b signaling. Our results demonstrate that mesenchymal Fgf10 regulates the epithelial expression of Shh, which in turn signals back to the mesenchyme. This was confirmed by demonstrating that cell proliferation is decreased not only in the palatal epithelium but also in the mesenchyme of Fgfr2b(-/-) mice. These results reveal a new role for Fgf signaling in mammalian palate development. We show that coordinated epithelial-mesenchymal interactions are essential during the initial stages of palate development and require an Fgf-Shh signaling network.