Key Laboratory of Molecular and Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
PLoS Genet. 2010 Aug 12;6(8):e1001056. doi: 10.1371/journal.pgen.1001056.
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.
理解神经系统的组织一直是一个挑战，其中之一就是确定轴突导向分子如何控制轴突的生长。通过一个无偏的遗传筛选，我们鉴定到了一个保守的 Wnt 信号通路，该通路对于秀丽隐杆线虫 RME 头神经元的轴突前后（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、共同受体 CAM-1/Ror 和下游成分 Dishevelled/DSH-1 组成。其中，CWN-2 作为轴突生长的局部吸引信号，其活性可以部分被其他 Wnts 替代，这表明空间分布在 Wnts 的功能特异性中起着作用。作为一个共同受体，CAM-1 在神经元中具有细胞自主性，并与 CFZ-2 和 MIG-1 一起将 Wnt 信号传递给下游效应物。酵母双杂交筛选鉴定出 DSH-1 是 CAM-1 的结合伴侣，这表明 CAM-1 可以通过与 DSH-1 的物理结合来促进 CWN-2/Wnt 信号传导。我们的研究揭示了 Wnt-Frz/Ror-Dsh 通路在调节神经元轴突前后生长中的重要作用。
