Brain assembly is hypothesized to begin when pioneer axons extend over non-neuronal cells, forming tracts guiding follower axons. Yet pioneer-neuron identities, their guidance substrates, and their interactions are not well understood. Here, using time-lapse embryonic imaging, genetics, protein-interaction, and functional studies, we uncover the early events of C. elegans brain assembly. We demonstrate that C. elegans glia are key for assembly initiation, guiding pioneer and follower axons using distinct signals. Pioneer sublateral neurons, with unique growth properties, anatomy, and innervation, cooperate with glia to mediate follower-axon guidance. We further identify a Chimaerin (CHIN-1)- Furin (KPC-1) double-mutant that severely disrupts assembly. CHIN-1 and KPC-1 function noncanonically, in glia and pioneer neurons, for guidance-cue trafficking. We exploit this bottleneck to define roles for glial Netrin and Semaphorin in pioneer- and follower-axon guidance, respectively, and for glial and pioneer-neuron Flamingo (CELSR) in follower-axon navigation. Taken together, our studies reveal previously undescribed glial roles in pioneer-axon guidance, suggesting conserved principles of brain assembly.

中文翻译：

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胶质细胞通过秀丽隐杆线虫的非经典的Chimaerin-Furin轴突引导来启动大脑组装。

据推测，当先驱轴突延伸到非神经元细胞上形成引导追随者轴突的管道时，便开始进行大脑组装。然而，关于先驱神经元的身份，其指导底物及其相互作用尚不十分了解。在这里，使用延时胚胎成像，遗传学，蛋白质相互作用和功能研究，我们发现了秀丽隐杆线虫大脑组装的早期事件。我们证明线虫胶质细胞是组装启动，指导先锋和追随者轴突使用不同信号的关键。具有独特的生长特性，解剖结构和神经支配能力的先锋性次侧神经元与神经胶质细胞协同作用，以介导跟随者轴突的引导。我们进一步确定严重破坏装配的奇马林（CHIN-1）-弗林（KPC-1）双突变体。CHIN-1和KPC-1在神经胶质细胞和先驱神经元中非典型地起作用，指导线索贩运。我们利用此瓶颈来分别定义神经胶质蛋白Netrin和Semaphorin在先驱和跟随者轴突导航中的作用，以及神经胶质和先驱中子火烈鸟（CELSR）在跟随者轴突导航中的作用。综上所述，我们的研究揭示了先驱轴突引导中先前未描述的神经胶质角色，暗示了大脑组装的保守原理。