Coordinated directional outgrowth and pattern formation by integration of Wnt5a and Fgf signaling in planar cell polarity
Coordinated directional outgrowth and pattern formation by integration of Wnt5a and Fgf signaling in planar cell polarity
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DOI：
10.1242/dev.163824
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发表时间：
2018-04-15
期刊：
影响因子：
4.6
通讯作者：
Yang, Yingzi
中科院分区：
文献类型：
--
作者：
Gao, Bo;Ajima, Rieko;Yang, Yingzi
复杂生物体的胚胎形态发生需要适当的模式和定向生长的调节。平面细胞极性(PCP)信号是一种重要的进化保守机制，通过它传递定向信息。PCP被认为是由全球线索建立的，最近的研究揭示了Wnt信号梯度在无脊椎动物和脊椎动物的上皮组织中的指导作用。然而，目前尚不清楚Wnt/PCP信号在形态发生过程中是否与胚胎模式协调调节。在这里，在小鼠发育的肢体中，我们发现肢体图案形成所需的顶端外胚层脊源性FGFs以Wnt5a依赖的方式调节沿近端远轴的PCP。我们用遗传证据证明了Wnt5a梯度作为一个全局线索在肢体间充质中建立PCP是有指导意义的，并且Wnt5a也发挥了允许的作用，允许成纤维细胞生长因子信号定向PCP。我们的结果表明，通过整合Wnt5a和成纤维细胞生长因子信号，肢体的形态发生受到定向生长和构图的协调调节。
Embryonic morphogenesis of a complex organism requires proper regulation of patterning and directional growth. Planar cell polarity (PCP) signaling is emerging as a crucial evolutionarily conserved mechanism whereby directional information is conveyed. PCP is thought to be established by global cues, and recent studies have revealed an instructive role of a Wnt signaling gradient in epithelial tissues of both invertebrates and vertebrates. However, it remains unclear whether Wnt/PCP signaling is regulated in a coordinated manner with embryonic patterning during morphogenesis. Here, in mouse developing limbs, we find that apical ectoderm ridge-derived Fgfs required for limb patterning regulate PCP along the proximaldistal axis in a Wnt5a-dependent manner. We demonstrate with genetic evidence that the Wnt5a gradient acts as a global cue that is instructive in establishing PCP in the limb mesenchyme, and that Wnt5a also plays a permissive role to allow Fgf signaling to orient PCP. Our results indicate that limb morphogenesis is regulated by coordination of directional growth and patterning through integration of Wnt5a and Fgf signaling.