C. elegans dystroglycan coordinates responsiveness of follower axons to dorsal/ventral and anterior/posterior guidance cues.
C. elegans dystroglycan coordinates responsiveness of follower axons to dorsal/ventral and anterior/posterior guidance cues.
复制标题
线虫肌营养不良聚糖协调跟随轴突对背侧/腹侧和前/后引导线索的反应性。
DOI：
10.1002/dneu.22011
复制
发表时间：
2012
影响因子：
3
通讯作者：
Kramer,JamesM
中科院分区：
文献类型：
--
作者：
Johnson,RobertP;Kramer,JamesM
后生动物的神经发育的特点是由先驱轴突建立最初的过程束，随后跟随轴突沿着这些先驱过程延伸。控制追随者沿着先锋路线延伸的保真度的机制在很大程度上是未知的。秀丽隐杆线虫，连接腰椎和肛前神经节的直角形腰椎连接的形成是先驱/追随者动力学的一个例子。我们发现糖醛酸异常同源物DGN‐1介导沿先锋轴突路线的跟随腰椎联合轴突延伸的保真度。indn‐1突变体，先锋PVQ神经元的轴突忠实地建立腰椎连接，但跟随腰椎神经元的轴突，如PVC，经常绕过腰椎连接，沿着斜向轨迹直接延伸到肛前神经节。相反，UNC - 6/netrin引导通路的破坏主要是扰乱PVQ腹侧引导，以先导腰椎联合。无论PVQ轴突的路径如何，DGN‐1 inunc‐6突变体的缺失对跟随轴突的引导具有数量上相似的影响，这表明DGN‐1不介导跟随/先锋粘附。相反，DGN - 1似乎阻断了跟随轴突对肛前神经节导向的引导线索的过早反应，这介导了腰椎联合轴突的腹前向重新定向。缺失分析表明，这些活性只需要最N端DGN‐1结构域。这些研究表明，糖醛酸调节生长锥对相互冲突的引导信号的反应对于限制跟随轴突向先行者铺设的束的延伸是重要的。©2011 Wiley期刊公司Develop Neurobiol, 2012
Neural development in metazoans is characterized by the establishment of initial process tracts by pioneer axons and the subsequent extension of follower axons along these pioneer processes. Mechanisms governing the fidelity of follower extension along pioneered routes are largely unknown. InC. elegans, formation of the right angle‐shaped lumbar commissure connecting the lumbar and preanal ganglia is an example of pioneer/follower dynamics. We find that the dystroglycan ortholog DGN‐1 mediates the fidelity of follower lumbar commissure axon extension along the pioneer axon route. Indgn‐1mutants, the axon of the pioneer PVQ neuron faithfully establishes the lumbar commissure, but axons of follower lumbar neurons, such as PVC, frequently bypass the lumbar commissure and extend along an oblique trajectory directly toward the preanal ganglion. In contrast, disruption of the UNC‐6/netrin guidance pathway principally perturbs PVQ ventral guidance to pioneer the lumbar commissure. Loss of DGN‐1 inunc‐6 mutants has a quantitatively similar effect on follower axon guidance regardless of PVQ axon route, indicating that DGN‐1 does not mediate follower/pioneer adhesion. Instead, DGN‐1 appears to block premature responsiveness of follower axons to a preanal ganglion‐directed guidance cue, which mediates ventral‐to‐anterior reorientation of lumbar commissure axons. Deletion analysis shows that only the most N‐terminal DGN‐1 domain is required for these activities. These studies suggest that dystroglycan modulation of growth cone responsiveness to conflicting guidance cues is important for restricting follower axon extension to the tracts laid down by pioneers. © 2011 Wiley Periodicals, Inc. Develop Neurobiol, 2012