Protocadherin-Mediated Cell Repulsion Controls the Central Topography and Efferent Projections of the Abducens Nucleus.,Cell Reports

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Protocadherin-Mediated Cell Repulsion Controls the Central Topography and Efferent Projections of the Abducens Nucleus.
Cell Reports ( IF 7.5 ) Pub Date : 2018-08-07 , DOI: 10.1016/j.celrep.2018.07.024
Kazuhide Asakawa ₁ , Koichi Kawakami ₁

Affiliation

Cranial motor nuclei in the brainstem innervate diverse types of head and neck muscles. Failure in establishing these neuromuscular connections causes congenital cranial dysinnervation disorders (CCDDs) characterized by abnormal craniofacial movements. However, mechanisms that link cranial motor nuclei to target muscles are poorly understood at the molecular level. Here, we report that protocadherin-mediated repulsion mediates neuromuscular connection in the ocular motor system in zebrafish. We identify pools of abducens motor neurons that are topographically arranged according to soma size and convergently innervate a single muscle. Disruptions of Duane retraction syndrome-associated transcription factors reveal that these neurons require Mafba/MAFB, but not Sall4/SALL4, for differentiation. Furthermore, genetic perturbations of Pcdh17/protocadherin-17 result in defective axon growth and soma clumping, thereby abolishing neuromuscular connectivity. Our results suggest that protocadherin-mediated repulsion forms the central topography and efferent projection pattern of the abducens nucleus following Mafba-dependent specification and imply potential involvement of protocadherins in CCDD etiology.

中文翻译：

钙粘蛋白原介导的细胞排斥控制外展核的中央地形和传出的投射。

脑干中的颅神经运动神经支配各种类型的头颈部肌肉。建立这些神经肌肉连接的失败会导致以颅面运动异常为特征的先天性颅神经失调症（CCDD）。但是，在分子水平上对将颅运动核与靶标肌肉联系起来的机制了解甚少。在这里，我们报道原钙粘蛋白介导的排斥作用介导斑马鱼眼运动系统中的神经肌肉连接。我们确定了根据躯体大小在地形上排列的外展肌运动神经元池，并会合神经支配单个肌肉。杜安回缩综合征相关转录因子的破坏表明，这些神经元需要Mafba / MAFB，但不需要Sall4 / SALL4进行分化。此外，Pcdh17 / protocadherin-17的遗传扰动导致轴突生长不良和体细胞团块化，从而消除了神经肌肉的连通性。我们的研究结果表明，原钙粘蛋白介导的排斥反应形成了依赖Mafba的规格的外展核的中心地形和传出的投射模式，暗示原钙粘蛋白可能参与了CCDD病因学。

更新日期：2018-08-08

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