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

被引:21
作者
Asakawa, Kazuhide [1 ,2 ]
Kawakami, Koichi [1 ,2 ]
机构
[1] Natl Inst Genet, Div Mol & Dev Biol, 1111 Yata, Mishima, Shizuoka 4118540, Japan
[2] Grad Univ Adv Studies SOKENDAI, Dept Genet, 1111 Yata, Mishima, Shizuoka 4118540, Japan
关键词
CRANIAL MOTOR-NEURONS; RADIAL RAY SYNDROME; OKIHIRO-SYNDROME; AXON GUIDANCE; HINDBRAIN SEGMENTATION; EXTRAOCULAR-MUSCLES; RETRACTION SYNDROME; INNER-EAR; ZEBRAFISH; MOTONEURONS;
D O I
10.1016/j.celrep.2018.07.024
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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. 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 Sa114/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.
引用
收藏
页码:1562 / 1572
页数:11
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