Cadherins regulate nuclear topography and function of developing ocular motor circuitry.
Cadherins regulate nuclear topography and function of developing ocular motor circuitry.
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DOI：
10.7554/elife.56725
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发表时间：
2020-10-01
期刊：
影响因子：
7.7
通讯作者：
Guthrie S
中科院分区：
文献类型：
--
作者：
Knüfer A;Diana G;Walsh GS;Clarke JD;Guthrie S
在脊椎动物中枢神经系统中，功能相关的神经元（包括脑干的颅运动神经元）的组通常被组织为核。对于核拓扑结构和电路功能出现的分子机制知之甚少。在这里，我们调查的作用，钙粘蛋白介导的粘附在斑马鱼眼运动（亚）核的发展。我们发现，发展中的眼运动（亚）核差异表达经典钙粘蛋白。干扰这些神经元中的钙粘蛋白功能会导致神经元定位的明显缺陷，包括背侧细胞的分散和腹侧亚核的对侧迁移缺陷。此外，我们发现，钙粘蛋白介导的相邻亚核之间的相互作用是至关重要的亚核位置。我们还发现，破坏背侧眼神经元中的钙粘蛋白粘附性损害幼虫视动反射，这表明神经元聚集对于协调电路功能是重要的。我们的研究结果表明，钙粘蛋白调节颅运动神经元定位的不同方面，并建立亚核地形图和运动功能。
In the vertebrate central nervous system, groups of functionally related neurons, including cranial motor neurons of the brainstem, are frequently organised as nuclei. The molecular mechanisms governing the emergence of nuclear topography and circuit function are poorly understood. Here we investigate the role of cadherin-mediated adhesion in the development of zebrafish ocular motor (sub)nuclei. We find that developing ocular motor (sub)nuclei differentially express classical cadherins. Perturbing cadherin function in these neurons results in distinct defects in neuronal positioning, including scattering of dorsal cells and defective contralateral migration of ventral subnuclei. In addition, we show that cadherin-mediated interactions between adjacent subnuclei are critical for subnucleus position. We also find that disrupting cadherin adhesivity in dorsal oculomotor neurons impairs the larval optokinetic reflex, suggesting that neuronal clustering is important for co-ordinating circuit function. Our findings reveal that cadherins regulate distinct aspects of cranial motor neuron positioning and establish subnuclear topography and motor function.