Meltzer Hagar, Schuldiner Oren
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Department of Molecular Neuroscience, Weizmann Institute of Science, Rehovot, Israel.
Front Neurosci. 2022 May 12;16:897706. doi: 10.3389/fnins.2022.897706. eCollection 2022.
Developmental neuronal remodeling is required for shaping the precise connectivity of the mature nervous system. Remodeling involves pruning of exuberant neural connections, often followed by regrowth of adult-specific ones, as a strategy to refine neural circuits. Errors in remodeling are associated with neurodevelopmental disorders such as schizophrenia and autism. Despite its fundamental nature, our understanding of the mechanisms governing neuronal remodeling is far from complete. Specifically, how precise spatiotemporal control of remodeling and rewiring is achieved is largely unknown. In recent years, cell adhesion molecules (CAMs), and other cell surface and secreted proteins of various families, have been implicated in processes of neurite pruning and wiring specificity during circuit reassembly. Here, we review some of the known as well as speculated roles of CAMs in these processes, highlighting recent advances in uncovering spatiotemporal aspects of regulation. Our focus is on the fruit fly , which is emerging as a powerful model in the field, due to the extensive, well-characterized and stereotypic remodeling events occurring throughout its nervous system during metamorphosis, combined with the wide and constantly growing toolkit to identify CAM binding and resulting cellular interactions . We believe that its many advantages pose as a leading candidate for future breakthroughs in the field of neuronal remodeling in general, and spatiotemporal control by CAMs specifically.
发育性神经元重塑是塑造成熟神经系统精确连接所必需的。重塑过程包括修剪过度生长的神经连接,随后通常会重新生长出成年特异性的连接,以此作为优化神经回路的一种策略。重塑过程中的错误与精神分裂症和自闭症等神经发育障碍有关。尽管其具有基础性本质,但我们对神经元重塑机制的理解还远远不够完整。具体而言,重塑和重新布线的精确时空控制是如何实现的,在很大程度上尚不清楚。近年来,细胞粘附分子(CAMs)以及其他不同家族的细胞表面和分泌蛋白,已被证明与神经回路重组过程中的神经突修剪和布线特异性有关。在这里,我们回顾了CAMs在这些过程中已知的以及推测的作用,突出了在揭示调控的时空方面的最新进展。我们关注的是果蝇,由于其在变态发育过程中整个神经系统会发生广泛、特征明确且刻板的重塑事件,再加上用于识别CAM结合及由此产生的细胞相互作用的广泛且不断增加的工具集,果蝇正成为该领域一个强大的模型。我们相信,果蝇的诸多优势使其成为神经元重塑领域,特别是CAMs介导的时空控制方面未来取得突破的主要候选对象。