Planar cell polarity signaling guides cochlear innervation.
Planar cell polarity signaling guides cochlear innervation.
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DOI：
10.1016/j.ydbio.2022.03.005
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发表时间：
2022-06
影响因子：
2.7
通讯作者：
Deans, Michael R.
中科院分区：
文献类型：
--
作者：
Deans, Michael R.
核心平面细胞极性（PCP）蛋白与响应Wnt配体的生长锥转向机制有关，并指导神经元、神经上皮和支持细胞的细胞组织和平面极性，其中许多细胞也是生长锥导航的底物。小鼠的遗传操作进一步证明，沿迁移路径的PCP蛋白可以对生长锥转向和神经元迁移产生非细胞自主影响。例如，在耳蜗中，II型螺旋神经节神经元（SGN）的外周轴突产生的独特的90度转弯依赖于PCP蛋白Vangl2和卷曲受体Fzd3和Fzd6。当从轴突转向起始位点的非神经元支持细胞中去除相应的基因时，轴突转向的结果是随机的。综上所述，这些观察结果表明，这些生长锥导航的耳蜗环境的平面极化发展或组织对寻路和轴突投射有实质性的影响。目前仍未解决的问题是，耳蜗支持细胞的平面极化如何影响生长锥行为、轴突轨迹和连通性。可能包括作为物理导向的细胞的先验结构极化，这些细胞内轴突导向信号的极化分布，或支持细胞和导航生长锥之间的直接细胞间PCP信号。面神经枝运动神经元（FBMN）的尾侧迁移同样依赖于PCP蛋白在神经上皮细胞基质中的平面极化分布。这提出了一个更广泛的问题：细胞沿生长锥轨迹的平面极化是否可能作为轴突引导的一般机制，或者这种机制是否是耳蜗特有的特殊适应。
Core planar cell polarity (PCP) proteins are linked to mechanisms of growth cone turning in response to Wnt ligands and direct the cellular organization and planar polarity of neurons, neuroepithelia and supporting cells, many of which are also the substrates along which growth cones navigate. Genetic manipulations in the mouse further demonstrate that PCP proteins along the migratory path can have a non-cell autonomous influence on growth cone turning and neuronal migration. For example, in the cochlea a distinctive 90-degree turn made by the peripheral axons of type II Spiral Ganglion Neurons (SGN) is dependent upon the PCP protein Vangl2 and the Frizzled receptors Fzd3 and Fzd6. When the corresponding genes are removed from non-neuronal supporting cells at the initial site of axon turning, the outcome of the turn is randomized. Together these observations demonstrate that the planar polarized development or organization of the cochlear environment through which these growth cones navigate has a substantive impact on pathfinding and axon projections. The outstanding question remains how planar polarization of cochlear supporting cells contributes to growth cone behavior, axonal trajectories and connectivity. Possibilities include the a priori structural polarization of cells that act as physical guides, the polarized distribution of axon guidance cues within these cells, or direct intercellular PCP signaling between supporting cells and navigating growth cones. The caudal migration of facial branchiomotor neurons (FBMN) is similarly dependent upon the planar polarized distribution of PCP proteins in the neuroepithelial cell substrate along which they migrate. This raises the broader question of whether planar polarization of cells along a growth cone’s trajectory might contribute as a general mechanism of axon guidance, or whether this mechanism is a specialized adaptation unique to the cochlea.
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