Distinct roles for Robo2 in the regulation of axon and dendrite growth by retinal ganglion cells
Distinct roles for Robo2 in the regulation of axon and dendrite growth by retinal ganglion cells
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DOI：
10.1016/j.mod.2009.11.002
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发表时间：
2010-01-01
影响因子：
2.6
通讯作者：
McFarlane, Sarah
中科院分区：
文献类型：
--
作者：
Hocking, Jennifer C.;Hehr, Carrie L.;McFarlane, Sarah
引导因子作用于生长中的轴突尖端，引导其到达目标。然而，这些分子在控制从轴突细胞体延伸出来的树突中所起的作用尚不清楚。裂缝，通过它们的机器人受体，引导许多类型的轴突，包括视网膜神经节细胞（RGCs）。在这里，我们评估和对比了狭缝/Robo信号在非洲爪蟾RGCs延伸的轴突和树突生长和引导中的作用。当爪蟾RGCs扩展树突时，它们表达robo2和robo3，而在RGCs和邻近的内核层中表达slit1和slit2。有趣的是，我们关于rob2 （dnRobo2）和Robo3 （dnRobo3）的反义敲除和显性阴性形式的功能数据表明，Slit/Robo信号在RGC树突引导中没有作用，相反，它是刺激树突分支所必需的，主要通过Robo2。我们的体外培养数据表明，狭缝是参与配体。相比之下，dnRobo2和dnRobo3均抑制轴突的延伸，并导致一些轴突的错误路由。基于这些数据，我们提出Robo信号在同一细胞的轴突和树突中可能具有不同的功能，并且Robo受体的特定组合可能是这些差异的基础。在树突中，Slit通过Robo2作为分支/生长因子，但不作为引导因子，而Robo2和Robo3在轴突中协同作用，介导轴突相互作用，并作为引导因子响应Slit。这些数据强调了有限数量的外部因素调节轴突和树突不同形态的可能性。2009爱思唯尔爱尔兰有限公司版权所有。
Guidance factors act on the tip of a growing axon to direct it to its target. What role these molecules play, however, in the control of the dendrites that extend from that axon's cell body is poorly understood. Slits, through their Robo receptors, guide many types of axons, including those of retinal ganglion cells (RGCs). Here we assess and contrast the role of Slit/Robo signalling in the growth and guidance of the axon and dendrites extended by RGCs in Xenopus laevis. As Xenopus RGCs extend dendrites, they express robo2 and robo3, while slit1 and slit2 are expressed in RGCs and in the adjacent inner nuclear layer. Interestingly, our functional data with antisense knockdown and dominant negative forms of Robo2 (dnRobo2) and Robo3 (dnRobo3) indicate that Slit/Robo signalling has no role in RGC dendrite guidance, and instead is necessary to stimulate dendrite branching, primarily via Robo2. Our in vitro culture data argue that Slits are the ligands involved. In contrast, both dnRobo2 and dnRobo3 inhibited the extension of axons and caused the misrouting of some axons. Based on these data, we propose that Robo signalling can have distinct functions in the axon and dendrites of the same cell, and that the specific combinations of Robo receptors could underlie these differences. Slit acts via Robo2 in dendrites as a branching/growth factor but not in guidance, while Robo2 and Robo3 function in concert in axons to mediate axonal interactions and respond to Slits as guidance factors. These data underscore the likelihood that a limited number of extrinsic factors regulate the distinct morphologies of axons and dendrites. (C) 2009 Elsevier Ireland Ltd. All rights reserved.