School of Life Sciences, Keele University, Keele, Staffordshire, ST5 5BG, UK.
Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA 98101, USA.
Development. 2024 Sep 1;151(17). doi: 10.1242/dev.202945. Epub 2024 Sep 13.
Spatially and temporally accurate termination of axon outgrowth, a process called axon termination, is required for efficient, precise nervous system construction and wiring. The mechanosensory neurons that sense low-threshold mechanical stimulation or gentle touch have proven exceptionally valuable for studying axon termination over the past 40 years. In this Review, we discuss progress made in deciphering the molecular and genetic mechanisms that govern axon termination in touch receptor neurons. Findings across model organisms, including Caenorhabditis elegans, Drosophila, zebrafish and mice, have revealed that complex signaling is required for termination with conserved principles and players beginning to surface. A key emerging theme is that axon termination is mediated by complex signaling networks that include ubiquitin ligase signaling hubs, kinase cascades, transcription factors, guidance/adhesion receptors and growth factors. Here, we begin a discussion about how these signaling networks could represent termination codes that trigger cessation of axon outgrowth in different species and types of mechanosensory neurons.
轴突生长的时空精确终止,即轴突终止过程,对于高效、精确的神经系统构建和布线是必需的。在过去的 40 年中,能够感知低阈值机械刺激或轻柔触摸的机械感觉神经元已被证明在研究轴突终止方面具有非常重要的价值。在这篇综述中,我们讨论了在破译控制触感器神经元轴突终止的分子和遗传机制方面取得的进展。包括秀丽隐杆线虫、果蝇、斑马鱼和小鼠在内的多种模式生物的研究结果表明,复杂的信号转导对于保守的原理和参与者的出现是终止所必需的。一个关键的新兴主题是,轴突终止是由包括泛素连接酶信号枢纽、激酶级联、转录因子、导向/粘附受体和生长因子在内的复杂信号网络介导的。在这里,我们开始讨论这些信号网络如何代表终止代码,这些代码可以在不同物种和不同类型的机械感觉神经元中触发轴突生长的停止。