Isbister C M, Tsai A, Wong S T, Kolodkin A L, O'Connor T P
Program in Neuroscience, Department of Anatomy, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada.
Development. 1999 May;126(9):2007-19. doi: 10.1242/dev.126.9.2007.
From the initial stages of axon outgrowth to the formation of a functioning synapse, neuronal growth cones continuously integrate and respond to multiple guidance cues. To investigate the role of semaphorins in the establishment of appropriate axon trajectories, we have characterized a novel secreted semaphorin in grasshopper, gSema 2a. Sema 2a is expressed in a gradient in the developing limb bud epithelium during Ti pioneer axon outgrowth. We demonstrate that Sema 2a acts as chemorepulsive guidance molecule critical for axon fasciculation and for determining both the initial direction and subsequent pathfinding events of the Ti axon projection. Interestingly, simultaneous perturbation of both secreted Sema 2a and transmembrane Sema I results in a broader range and increased incidence of abnormal Ti pioneer axon phenotypes, indicating that different semaphorin family members can provide functionally distinct guidance information to the same growth cone in vivo.
从轴突生长的初始阶段到功能性突触的形成，神经元生长锥不断整合并对多种导向线索做出反应。为了研究信号素在建立合适轴突轨迹中的作用，我们鉴定了一种在蝗虫中发现的新型分泌型信号素，即gSema 2a。在Ti先驱轴突生长期间，Sema 2a在发育中的肢芽上皮细胞中呈梯度表达。我们证明，Sema 2a作为一种化学排斥性导向分子，对于轴突成束以及确定Ti轴突投射的初始方向和后续路径寻找事件至关重要。有趣的是，同时干扰分泌型Sema 2a和跨膜型Sema I会导致Ti先驱轴突异常表型的范围更广且发生率增加，这表明不同的信号素家族成员可以在体内为同一个生长锥提供功能上不同的导向信息。
