Mushroom body defect is required in parallel to Netrin for midline axon guidance in Drosophila.
Mushroom body defect is required in parallel to Netrin for midline axon guidance in Drosophila.
复制标题
与Netrin平行需要蘑菇体缺陷，以进行果蝇中线轴突指导。
DOI：
10.1242/dev.129684
复制
发表时间：
2016-03-15
期刊：
影响因子：
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通讯作者：
Mitchell KJ
中科院分区：
文献类型：
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作者：
Cate MS;Gajendra S;Alsbury S;Raabe T;Tear G;Mitchell KJ
中枢神经系统内许多神经元的突起最初指向或远离位于中线的细胞。最近的遗传学证据表明，对保守的Netrin吸引剂和缝隙驱避剂的差异敏感性的简单模型不足以解释所有轴突在中线的引导。在果蝇胚胎腹神经索中，在缺乏Netrin基因(NetA和NetB)或其受体受损的情况下，许多轴突仍穿过中线。在这里，我们表明蘑菇体缺陷(MUD)的突变极大地增强了Netrin或疲劳突变体的表型，导致更多的轴突无法穿过中线，尽管MUD的突变本身影响很小。这表明，MUD编码一种与NUMA和LIN-5同源的微管结合卷曲蛋白，是平行作用促进中线交叉的Netrin非依赖性途径的重要组成部分。我们证明了Mud在轴突引导中的这种新作用是独立于其先前描述的在神经前体发育中的作用的。这些研究确定了一条平行的控制果蝇中线引导的途径，并强调了Mud可能作用于Frizzled河下游以辅助轴突引导的一个新角色。摘要：MUD/NUMA/LIN-5是一种信号转导元件，可能作用于Frizzled区下游，介导Netrin非依赖性轴突导向中线。
The outgrowth of many neurons within the central nervous system is initially directed towards or away from the cells lying at the midline. Recent genetic evidence suggests that a simple model of differential sensitivity to the conserved Netrin attractants and Slit repellents is insufficient to explain the guidance of all axons at the midline. In the Drosophila embryonic ventral nerve cord, many axons still cross the midline in the absence of the Netrin genes (NetA and NetB) or their receptor frazzled. Here we show that mutation of mushroom body defect (mud) dramatically enhances the phenotype of Netrin or frazzled mutants, resulting in many more axons failing to cross the midline, although mutations in mud alone have little effect. This suggests that mud, which encodes a microtubule-binding coiled-coil protein homologous to NuMA and LIN-5, is an essential component of a Netrin-independent pathway that acts in parallel to promote midline crossing. We demonstrate that this novel role of Mud in axon guidance is independent of its previously described role in neural precursor development. These studies identify a parallel pathway controlling midline guidance in Drosophila and highlight a novel role for Mud potentially acting downstream of Frizzled to aid axon guidance. Summary: Mud/NuMA/LIN-5 is a signal transduction component, potentially acting downstream of Frizzled to mediate netrin-independent axon guidance towards the midline.