Spillane Mirela, Gallo Gianluca
Shriners Hospitals Pediatric Research Center; Center for Neural Repair and Rehabilitation; Temple University; Department of Anatomy and Cell Biology; Philadelphia, PA USA.
Small GTPases. 2014;5:e27974. doi: 10.4161/sgtp.27974. Epub 2014 Mar 11.
Development of the nervous system requires efficient extension and guidance of axons and dendrites culminating in synapse formation. Axonal growth and navigation during embryogenesis are controlled by extracellular cues. Many of the same extracellular signals also regulate axonal branching. The emergence of collateral branches from the axon augments the complexity of nervous system innervation and provides an additional mechanism for target selection. Rho-family GTPases play an important role in regulating intracellular cytoskeletal and signaling pathways that facilitate axonal morphological changes. RhoA/G and Rac1 GTPase functions are complex and they can induce or inhibit branch formation, depending on neuronal type, cell context or signaling mechanisms. Evidence of a role of Cdc42 in axon branching is mostly lacking. In contrast, Rac3 has thus far been implicated in the regulation of axon branching. Future analysis of the upstream regulators and downstream effectors mediating the effects of Rho-family GTPase will provide insights into the cellular processes effected, and shed light on the sometimes opposing roles of these GTPases in the regulation of axon branching.
神经系统的发育需要轴突和树突高效地延伸与导向，最终形成突触。胚胎发育过程中轴突的生长和导航受细胞外信号的控制。许多相同的细胞外信号也调节轴突分支。轴突侧支的出现增加了神经系统支配的复杂性，并为靶标选择提供了一种额外机制。Rho家族小G蛋白在调节促进轴突形态变化的细胞内细胞骨架和信号通路中起重要作用。RhoA/G和Rac1小G蛋白的功能很复杂，它们可诱导或抑制分支形成，这取决于神经元类型、细胞环境或信号传导机制。目前大多缺乏Cdc42在轴突分支中发挥作用的证据。相比之下，Rac3迄今已被认为参与轴突分支的调节。对介导Rho家族小G蛋白作用的上游调节因子和下游效应器的未来分析，将为所影响的细胞过程提供见解，并阐明这些小G蛋白在轴突分支调节中有时相反的作用。
