Institute of Toxicology and Genetics (ITG), Karlsruhe Institute of Technology (KIT), Hermann-von-Helmholtz Platz 1, 76021 Karlsruhe, Germany.
1] Steinbuch Center for Computing (SCC), Karlsruhe Institute of Technology (KIT), Hermann-von-Helmholtz Platz 1, 76021 Karlsruhe, Germany [2] Department of Physics, Karlsruhe Institute of Technology (KIT), Hermann-von-Helmholtz Platz 1, 76021 Karlsruhe, Germany.
Nat Commun. 2015 Jan 5;6:5846. doi: 10.1038/ncomms6846.
Paracrine Wnt/β-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.
旁分泌 Wnt/β-连环蛋白信号在发育过程、组织再生和干细胞调节中很重要。Wnt 蛋白是形态发生素,它们在响应组织中形成浓度梯度。目前对于脊椎动物中这些脂修饰信号蛋白的运输机制知之甚少。在这里,我们表明 Wnt8a 是通过基于肌动蛋白的丝状伪足运输的,以与反应细胞接触并在斑马鱼神经板形成过程中激活信号。Cdc42/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增加了 Wnt 的有效信号范围。一致地,丝状伪足的减少导致配体的分布受限和信号范围有限。通过模拟,我们提供了证据表明 Wnt 的这种短距离运输系统具有长距离信号功能。事实上,我们表明 Wnt8a 的基于丝状伪足的运输系统控制了脊椎动物原肠胚形成过程中神经板的前后模式形成。