A Wnt-Frz/Ror-Dsh Pathway Regulates Neurite Outgrowth in Caenorhabditis elegans
A Wnt-Frz/Ror-Dsh Pathway Regulates Neurite Outgrowth in Caenorhabditis elegans
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Wnt-Frz/Ror-Dsh 通路调节秀丽隐杆线虫神经突生长
DOI：
10.1371/journal.pgen.1001056
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发表时间：
2010-08-01
期刊：
影响因子：
4.5
通讯作者：
Ding, Mei
中科院分区：
文献类型：
--
作者：
Song, Song;Zhang, Bo;Ding, Mei
要了解神经系统的组织结构，其中一个挑战是确定轴突引导分子如何管理轴突生长。通过无偏见的遗传筛选，我们发现了一条保守的Wnt通路，该通路对秀丽线虫RME头运动神经元突起的前后部(A/P)生长至关重要。该通路由Wnt配体CWN-2、Frizzled受体CFZ-2和MIG-1、共受体CAM-1/ROR和下游成分Disheveled/DSH-1组成。其中，CWN-2可作为神经突起生长的局部信号，其活性可部分替代其他WNT，提示空间分布在WNT的功能特异性中起一定作用。作为辅助受体，CAM-1在神经元中以细胞自主的方式发挥作用，并与CFZ-2和MIG-1一起将Wnt信号传递给下游的效应器。酵母双杂交筛选发现DSH-1是CAM-1的结合伙伴，表明CAM-1可能通过与DSH-1的物理结合来促进CWN-2/WNT信号转导。我们的研究揭示了Wnt-FRZ/Ror-Dsh通路在调节轴突A/P突起生长中的重要作用。
One of the challenges to understand the organization of the nervous system has been to determine how axon guidance molecules govern axon outgrowth. Through an unbiased genetic screen, we identified a conserved Wnt pathway which is crucial for anterior-posterior (A/P) outgrowth of neurites from RME head motor neurons in Caenorhabditis elegans. The pathway is composed of the Wnt ligand CWN-2, the Frizzled receptors CFZ-2 and MIG-1, the co-receptor CAM-1/Ror, and the downstream component Dishevelled/DSH-1. Among these, CWN-2 acts as a local attractive cue for neurite outgrowth, and its activity can be partially substituted with other Wnts, suggesting that spatial distribution plays a role in the functional specificity of Wnts. As a co-receptor, CAM-1 functions cell-autonomously in neurons and, together with CFZ-2 and MIG-1, transmits the Wnt signal to downstream effectors. Yeast two-hybrid screening identified DSH-1 as a binding partner for CAM-1, indicating that CAM-1 could facilitate CWN-2/Wnt signaling by its physical association with DSH-1. Our study reveals an important role of a Wnt-Frz/Ror-Dsh pathway in regulating neurite A/P outgrowth.