SLIT 和 ROBO 介导的 commissural 轴突路径寻找的调节
中文名称
通路描述
commissural 轴突投射到板层状结构，受到其 DCC 受体与板层状结构细胞产生的 Netrin-1 (NTN1) 相互作用以及径向胶质细胞 (Dickson 和 Gilestro 2006) 和径向胶质细胞 (Dominici 等人 2017, Varadarajan 等人 2017) 的吸引。一旦轴突进入板层状结构，它必须有效地在相反侧排出。从吸引到排斥的转换允许 commissural 轴突进入 CNS 正中并随后离开。基于 Xenopus 神经元的研究和酵母双杂交筛选，观察到轴突对 netrins 的吸引反应被 ROBO 的激活所沉默。SLIT 结合 ROBO 与 DCC 结合，阻止其向 netrin 传递吸引反应。轴突对 SLIT 排斥作用的敏感性不仅取决于排斥性 SLIT 受体 (ROBO1 和 ROBO2)，还受到 ROBO3 表达的影响，ROBO3 是一种抑制 ROBO1 和 ROBO2 活性的 SLIT 受体。在穿过正中后， commissural 轴突下调 ROBO3 的表达并上调 ROBO1/ROBO2 的表达（综述 Dickson 和 Gilestro, 2006）。ROBO3 的两个转录变体 ROBO3.1 和 ROBO3.2 被认为在中线穿越中发挥不同的作用。ROBO3.1 在穿越前和穿越 commissural 轴突中表达，而 ROBO3.2 由替代剪接产生，在穿过中线后表达，被认为阻止中线再穿越 (Chen 等人 2008)。除了 SLITs 外，一种分泌的配体 NELL2 也作为轴突引导线索起作用，通过作用于 ROBO3 受体帮助引导 commissural 轴突到正中。ROBO3.1 和 ROBO3.2 都可以结合分泌的配体 NELL2。穿越前 commissural 轴突 (表达 ROBO3.1) 被 NELL2 排斥。穿越后轴突 (表达 ROBO3.2) 不被 NELL2 排斥 (Jaworski 等人 2015)。
英文描述
Regulation of commissural axon pathfinding by SLIT and ROBO Commissural axons project to the floor plate, attracted by the interaction of their DCC receptors with Netrin-1 (NTN1) produced by floor plate cells (Dickson and Gilestro 2006) and radial glia (Dominici et al. 2017, Varadarajan et al. 2017). Once an axon enters the floor plate, it must be efficiently expelled on the contralateral side. A switch from attraction to repulsion allows commissural axons to enter and then leave the CNS midline. Based on studies in Xenopus neurons and by yeast two hybrid screens, it is observed that the attractive response of axons to netrins is silenced by activation of ROBO. SLIT bound ROBO binds to DCC, preventing it from transducing an attractive response to netrin. The sensitivity of axons to the repulsive action of SLIT does not only depend on repulsive SLIT receptors (ROBO1 and ROBO2), but is also influenced by expression of ROBO3, a SLIT receptor that suppresses the activity of ROBO1 and ROBO2. Upon crossing the midline, commissural axons downregulate expression of ROBO3 and increase expression of ROBO1/ROBO2 (reviewed by Dickson and Gilestro, 2006). Two transcript variants of ROBO3, ROBO3.1 and ROBO3.2 are considered to play different roles in midline crossing. ROBO3.1 is expressed in the pre-crossing and crossing commissural axons, while ROBO3.2, generated by alternative splicing, is expressed after midline crossing and thought to block midline re-crossing (Chen et al. 2008). In addition to SLITs, a secreted ligand NELL2 also acts as an axonal guidance cue that, by acting through ROBO3 receptors, helps to steer commissural axons to the midline. Both ROBO3.1 and ROBO3.2 can bind to a secreted ligand NELL2. Pre-crossing commissural axons, which express ROBO3.1, are repelled by NELL2. Post-crossing axons, which express ROBO3.2 are not repelled by NELL2 (Jaworski et al. 2015). .
所含基因
9 个基因