Filopodia-based Wnt transport during vertebrate tissue patterning
Filopodia-based Wnt transport during vertebrate tissue patterning
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DOI：
10.1038/ncomms6846
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发表时间：
2015-01-01
影响因子：
16.6
通讯作者：
Scholpp, Steffen
中科院分区：
文献类型：
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作者：
Stanganello, Eliana;Hagemann, Anja I. H.;Scholpp, Steffen
旁分泌Wnt/β-连环蛋白信号传导在发育过程、组织再生和干细胞调节中是重要的。Wnt蛋白是形态发生素，其在响应组织中形成浓度梯度。关于这些脂质修饰的信号蛋白在脊椎动物中的转运机制知之甚少。在这里，我们表明，Wnt 8a是运输肌动蛋白为基础的丝状伪足接触响应细胞和激活信号在斑马鱼神经板形成。Cdc 42/N-Wasp调节这些Wnt阳性丝状伪足的形成。丝状伪足的增强形成通过促进扩散来增加Wnt的有效信号传导范围。一致地，丝状伪足的减少导致配体的分布受限和信号传导范围受限。使用模拟，我们提供的证据表明，这样一个短距离运输系统的Wnt具有远程信号功能。事实上，我们表明，Wnt 8a的丝状伪足为基础的运输系统控制前后图案的神经板在脊椎动物原肠胚形成。
Paracrine Wnt/beta-catenin signalling is important during developmental processes, tissue regeneration and stem cell regulation. Wnt proteins are morphogens, which form concentration gradients across responsive tissues. Little is known about the transport mechanism for these lipid-modified signalling proteins in vertebrates. Here we show that Wnt8a is transported on actin-based filopodia to contact responding cells and activate signalling during neural plate formation in zebrafish. Cdc42/N-Wasp regulates the formation of these Wnt-positive filopodia. Enhanced formation of filopodia increases the effective signalling range of Wnt by facilitating spreading. Consistently, reduction in filopodia leads to a restricted distribution of the ligand and a limited signalling range. Using a simulation, we provide evidence that such a short-range transport system for Wnt has a long-range signalling function. Indeed, we show that a filopodia-based transport system for Wnt8a controls anteroposterior patterning of the neural plate during vertebrate gastrulation.