PCP Signaling between Migrating Neurons and their Planar-Polarized Neuroepithelial Environment Controls Filopodial Dynamics and Directional Migration.
PCP Signaling between Migrating Neurons and their Planar-Polarized Neuroepithelial Environment Controls Filopodial Dynamics and Directional Migration.
复制标题
DOI：
10.1371/journal.pgen.1005934
复制
发表时间：
2016-03
期刊：
影响因子：
4.5
通讯作者：
Moens CB
中科院分区：
文献类型：
--
作者：
Davey CF;Mathewson AW;Moens CB
平面细胞极性（PCP）途径是一种细胞接触介导的机制，用于在相邻细胞之间传递极性信息。PCP的“核心成分”（Vangl，Fz，Pk，Dsh和Celsr）是必不可少的一些细胞迁移事件，包括面鳃神经元（FBMN）在斑马鱼和小鼠的后脑神经上皮平面的后迁移。虽然PCP信号极化静态上皮细胞的机制是很好的理解，PCP信号如何控制高度动态的过程，如神经元迁移仍然是一个重要的悬而未决的问题，因为PCP组件已被牵连在一系列定向细胞运动，特别是在脊椎动物的发展。在这里，通过系统地破坏PCP信号的菱形节限制的方式，我们表明，PCP信号是必需的FBMN和后脑菱形节4环境中的时间，当他们开始迁移。相应地，我们证明了PCP核心成分Vangl2和Fzd3a在后脑神经上皮中的平面极化定位，以及Vangl2在缩回FBMN丝状伪足尖端的瞬时定位。使用遗传嵌合体中FBMN的高分辨率时移成像，我们揭示了Fzd3a和Vangl2在调节FBMN分泌活性中的相反的细胞自主和非细胞自主功能。在FBMN内，Fzd3a需要稳定丝状伪足，而Vangl2具有拮抗性、不稳定性作用。然而，在迁移环境中，Fzd3a起到使FBMN丝状伪足不稳定的作用，而Vangl2具有稳定作用。总之，我们的研究结果表明，在平面极化的神经上皮环境和FBMN之间的PCP信号传导通过FBMN丝状伪足的选择性稳定来指导迁移的模型。平面细胞极性（PCP）是许多动物组织的共同特征。这种类型的极性在组织成上皮层的细胞中最为明显，其中PCP信号成分作用于组织平面中的细胞。尽管五氯苯酚在极化稳定上皮细胞中的功能最为人所知，但在动物发育和疾病中，细胞迁移的动态过程也需要五氯苯酚。本研究的目的是确定PCP如何控制细胞迁移。我们使用的迁移面鳃神经元在斑马鱼后脑，这需要几乎整个套件的PCP核心组件，以解决这个问题。我们提出的证据表明，PCP信号迁移神经元内，迁移神经元和细胞之间的迁移环境，促进迁移，通过调节丝状伪足动力学。我们的研究结果表明，广泛保守的PCP组件之间的相互作用控制细胞骨架在运动细胞和非运动上皮细胞一样。
The planar cell polarity (PCP) pathway is a cell-contact mediated mechanism for transmitting polarity information between neighboring cells. PCP “core components” (Vangl, Fz, Pk, Dsh, and Celsr) are essential for a number of cell migratory events including the posterior migration of facial branchiomotor neurons (FBMNs) in the plane of the hindbrain neuroepithelium in zebrafish and mice. While the mechanism by which PCP signaling polarizes static epithelial cells is well understood, how PCP signaling controls highly dynamic processes like neuronal migration remains an important outstanding question given that PCP components have been implicated in a range of directed cell movements, particularly during vertebrate development. Here, by systematically disrupting PCP signaling in a rhombomere-restricted manner we show that PCP signaling is required both within FBMNs and the hindbrain rhombomere 4 environment at the time when they initiate their migration. Correspondingly, we demonstrate planar polarized localization of PCP core components Vangl2 and Fzd3a in the hindbrain neuroepithelium, and transient localization of Vangl2 at the tips of retracting FBMN filopodia. Using high-resolution timelapse imaging of FBMNs in genetic chimeras we uncover opposing cell-autonomous and non-cell-autonomous functions for Fzd3a and Vangl2 in regulating FBMN protrusive activity. Within FBMNs, Fzd3a is required to stabilize filopodia while Vangl2 has an antagonistic, destabilizing role. However, in the migratory environment Fzd3a acts to destabilize FBMN filopodia while Vangl2 has a stabilizing role. Together, our findings suggest a model in which PCP signaling between the planar polarized neuroepithelial environment and FBMNs directs migration by the selective stabilization of FBMN filopodia. Planar cell polarity (PCP) is a common feature of many animal tissues. This type of polarity is most obvious in cells that are organized into epithelial sheets, where PCP signaling components act to orient cells in the plane of the tissue. Although, PCP is best understood for its function in polarizing stable epithelia, PCP is also required for the dynamic process of cell migration in animal development and disease. The goal of this study was to determine how PCP functions to control cell migration. We used the migration of facial branchiomotor neurons in the zebrafish hindbrain, which requires almost the entire suite of PCP core components, to address this question. We present evidence that PCP signaling within migrating neurons, and between migrating neurons and cells of their migratory environment promote migration by regulating filopodial dynamics. Our results suggest that broadly conserved interactions between PCP components control the cytoskeleton in motile cells and non-motile epithelia alike.