Avilés Evelyn C, Stoeckli Esther T
Institute of Molecular Life Sciences and Neuroscience Center Zurich, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland.
Dev Neurobiol. 2016 Feb;76(2):190-208. doi: 10.1002/dneu.22307. Epub 2015 Jul 3.
Morphogens have been identified as guidance cues for postcrossing commissural axons in the spinal cord. Shh has a dual effect on postcrossing commissural axons: a direct repellent effect mediated by Hhip as a receptor, and an indirect effect by shaping a Wnt activity gradient. Wnts were shown to be attractants for postcrossing commissural axons in both chicken and mouse embryos. In mouse, the effects of Wnts on axon guidance were concluded to depend on the planar cell polarity (PCP) pathway. Canonical Wnt signaling was excluded based on the absence of axon guidance defects in mice lacking Lrp6 which is an obligatory coreceptor for Fzd in canonical Wnt signaling. In the loss-of-function studies reported here, we confirmed a role for the PCP pathway in postcrossing commissural axon guidance also in the chicken embryo. However, taking advantage of the precise temporal control of gene silencing provided by in ovo RNAi, we demonstrate that canonical Wnt signaling is also required for proper guidance of postcrossing commissural axons in the developing spinal cord. Thus, axon guidance does not seem to depend on any one of the classical Wnt signaling pathways but rather involve a network of Wnt receptors and downstream components.
形态发生素已被确定为脊髓中交叉后连合轴突的引导线索。音猬因子（Shh）对交叉后连合轴突有双重作用：一种由Hhip作为受体介导的直接排斥作用，以及通过塑造Wnt活性梯度产生的间接作用。在鸡和小鼠胚胎中，Wnts均被证明是交叉后连合轴突的吸引剂。在小鼠中，Wnts对轴突导向的作用被认为取决于平面细胞极性（PCP）途径。基于缺乏Lrp6（经典Wnt信号通路中Fzd的必需共受体）的小鼠不存在轴突导向缺陷，经典Wnt信号传导被排除。在本文报道的功能丧失研究中，我们证实了PCP途径在鸡胚胎交叉后连合轴突导向中也发挥作用。然而，利用卵内RNA干扰提供的精确基因沉默时间控制，我们证明了经典Wnt信号传导对于发育中的脊髓中交叉后连合轴突的正确导向也是必需的。因此，轴突导向似乎并不依赖于任何一种经典的Wnt信号通路，而是涉及Wnt受体和下游成分的网络。
