Department of Chemistry and Molecular Biology, University of Gothenburg, 405 30, Sweden.
Faculty of Medicine Research Program Unit Translational Cancer Biology, University of Helsinki, FI-00014, Finland.
Genetics. 2017 Dec;207(4):1533-1545. doi: 10.1534/genetics.117.300375. Epub 2017 Oct 9.
The ventral nerve cord (VNC) consists of two asymmetric bundles of neurons and axons that are separated by the midline. How the axons are guided to stay on the correct sides of the midline remains poorly understood. Here we provide evidence that the conserved Wnt signaling pathway along with the Netrin and Robo pathways constitute a combinatorial code for midline guidance of PVP and PVQ axons that extend into the VNC. Combined loss of the Wnts CWN-1, CWN-2, and EGL-20 or loss of the Wnt receptor CAM-1 caused >70% of PVP and PVQ axons to inappropriately cross over from the left side to the right side. Loss of the Frizzled receptor LIN-17 or the planar cell polarity (PCP) protein VANG-1 also caused cross over defects that did not enhance those in the mutant, indicating that the proteins function together in midline guidance. Strong expression can be detected in the PVQs and the guidepost cell PVT that is located on the midline. However, only when is expressed in PVT are the crossover defects of PVP and PVQ rescued, showing that CAM-1 functions nonautonomously in PVT to prevent axons from crossing the midline.
腹神经索（VNC）由两个不对称的神经元和轴突束组成，它们被中线隔开。轴突如何被引导保持在中线的正确侧仍然知之甚少。在这里，我们提供的证据表明，保守的 Wnt 信号通路以及 Netrin 和 Robo 通路构成了 PVP 和 PVQ 轴突中线导向的组合密码，这些轴突延伸到 VNC。CWN-1、CWN-2 和 EGL-20 的 Wnt 缺失或 Wnt 受体 CAM-1 的缺失导致超过 70%的 PVP 和 PVQ 轴突不恰当地从左侧交叉到右侧。Frizzled 受体 LIN-17 或平面细胞极性（PCP）蛋白 VANG-1 的缺失也会导致交叉缺陷，但不会增强突变体中的缺陷，表明这些蛋白在中线导向中共同发挥作用。在位于中线的 PVQs 和路标细胞 PVT 中可以检测到强烈的 表达。然而，只有当 在 PVT 中表达时，PVP 和 PVQ 的交叉缺陷才会得到挽救，表明 CAM-1 在 PVT 中发挥非自主性作用以防止轴突穿过中线。
