A non-autonomous function of the core PCP protein VANGL2 directs peripheral axon turning in the developing cochlea
A non-autonomous function of the core PCP protein VANGL2 directs peripheral axon turning in the developing cochlea
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DOI：
10.1242/dev.159012
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发表时间：
2018-06-01
期刊：
影响因子：
4.6
通讯作者：
Deans, Michael R.
中科院分区：
文献类型：
--
作者：
Ghimire, Satish R.;Ratzan, Evan M.;Deans, Michael R.
耳蜗由神经元支配，这些神经元将声音信息从毛细胞传递到中枢听觉目标。其中的一个子集是II型螺旋神经节神经元，它具有伤害性特征，并有助于在极端噪声下提供神经保护的反馈回路。II型神经元以独特的90度转向耳蜗基底，与10-15个外毛细胞突触。我们证明这种轴突转向事件需要平面细胞极性（PCP）信号，并且在Vangl2和Celsr1敲除小鼠中被破坏，并且Vangl2从耳蜗非自主地作用到直接转向。此外，VANGL2不对称地分布在耳蜗支持细胞之间的细胞间连接处，并以一种模式允许它直接作为轴突引导信号。总之，这些数据揭示了PCP信号在轴突引导过程中的非自主功能发生在受神经支配的组织中，而不是导航生长锥。
The cochlea is innervated by neurons that relay sound information from hair cells to central auditory targets. A subset of these are the type II spiral ganglion neurons, which have nociceptive features and contribute to feedback circuits providing neuroprotection in extreme noise. Type II neurons make a distinctive 90 degrees turn towards the cochlear base to synapse with 10-15 outer hair cells. We demonstrate that this axon turning event requires planar cell polarity (PCP) signaling and is disrupted in Vangl2 and Celsr1 knockout mice, and that VANGL2 acts non-autonomously from the cochlea to direct turning. Moreover, VANGL2 is asymmetrically distributed at intercellular junctions between cochlear supporting cells, and in a pattern that could allow it to act directly as an axon guidance cue. Together, these data reveal a non-autonomous function for PCP signaling during axon guidance occurring in the tissue that is innervated, rather than the navigating growth cone.