Hamelin M, Zhou Y, Su M W, Scott I M, Culotti J G
Samuel Lunenfeld Research Institute of Mount Sinai Hospital, Toronto, Canada.
Nature. 1993 Jul 22;364(6435):327-30. doi: 10.1038/364327a0.
Growth cones in developing nervous systems encounter a sequence of extracellular cues during migration. In theory, a growth cone can navigate by selectively expressing or activating surface receptor(s) that recognize extracellular cues appropriate to each migratory phase. Using the simple Caenorhabditis elegans nervous system, we attempted to demonstrate that path selection by migrating growth cones can be predictably altered by ectopic expression of a single receptor. The unc-5 gene of C. elegans encodes a unique receptor of the immunoglobulin superfamily (UNC-5), required cell-autonomously to guide growth cone and mesodermal cell migrations in a dorsal direction on the epidermis. We report here that the UNC-5 receptor induces dorsally oriented axon trajectories when ectopically expressed in the touch receptor neurons which normally extend pioneer axons longitudinally or ventrally on the epidermis. These errant trajectories depend on unc-6, which encodes a putative epidermal path cue, just as normal dorsally oriented axon trajectories do (such as those of certain motor neurons), suggesting that UNC-5 acts to reorient the touch cell growth cones by using its normal guidance mechanisms. These results support previous evidence that UNC-5 and UNC-6 play instructive rules in guiding growth cone migrations on the epidermis in C. elegans, and indicate that pioneering growth cones, which normally migrate in different directions, may use equivalent intracellular signalling mechanisms for guidance.
发育中的神经系统中的生长锥在迁移过程中会遇到一系列细胞外信号。理论上,生长锥可以通过选择性地表达或激活识别适合每个迁移阶段的细胞外信号的表面受体来导航。利用简单的秀丽隐杆线虫神经系统,我们试图证明迁移的生长锥的路径选择可以通过单个受体的异位表达而被可预测地改变。秀丽隐杆线虫的unc-5基因编码免疫球蛋白超家族的一种独特受体(UNC-5),它在细胞自主的情况下是引导生长锥和中胚层细胞在表皮上沿背侧迁移所必需的。我们在此报告,当UNC-5受体在通常在表皮上纵向或腹侧延伸先驱轴突的触觉受体神经元中异位表达时,会诱导背向的轴突轨迹。这些错误的轨迹依赖于unc-6,unc-6编码一种假定的表皮路径信号,就像正常的背向轴突轨迹(如某些运动神经元的轨迹)一样,这表明UNC-5通过使用其正常的引导机制来重新定向触觉细胞生长锥。这些结果支持了先前的证据,即UNC-5和UNC-6在引导秀丽隐杆线虫表皮上的生长锥迁移中起指导作用,并表明通常向不同方向迁移的先驱生长锥可能使用等效的细胞内信号传导机制进行引导。