Department of Neurobiology, Stanford University, Stanford, CA 94305, USA.
Cell. 2013 Jul 18;154(2):351-64. doi: 10.1016/j.cell.2013.06.011.
Neuronal growth cones select synaptic partners through interactions with multiple cell surfaces in their environment. Many of these interactions are adhesive, yet it is unclear how growth cones integrate adhesive cues to direct their movements. Here, we examine the mechanisms that enable photoreceptors in the Drosophila visual system to choose synaptic partners. We demonstrate that the classical cadherin, N-cadherin, and an atypical cadherin, Flamingo, act redundantly to instruct the targeting choices made by every photoreceptor axon. These molecules gradually bias the spatial distribution of growth cone filopodia, polarizing each growth cone toward its future synaptic target before direct contact with the target occurs. We demonstrate that these molecules are localized to distinct subcellular domains and create a network of adhesive interactions distributed across many growth cones. Because this network comprises multiple redundant interactions, a complex wiring diagram can be constructed with extraordinary fidelity, suggesting a general principle.
神经元生长锥通过与环境中的多个细胞表面相互作用来选择突触伙伴。这些相互作用中有许多是黏附性的，但目前尚不清楚生长锥如何整合黏附性线索来指导其运动。在这里，我们研究了使果蝇视觉系统中的感光细胞选择突触伙伴的机制。我们证明经典钙黏蛋白 N-钙黏蛋白和非典型钙黏蛋白 Flamingo 冗余地作用以指示每个感光细胞轴突做出的靶向选择。这些分子逐渐偏向生长锥丝状伪足的空间分布，在与目标直接接触之前，使每个生长锥向其未来的突触目标极化。我们证明这些分子定位于不同的亚细胞区域，并在许多生长锥之间创建一个黏附相互作用网络。由于这个网络包含多个冗余的相互作用，可以用极高的精度构建一个复杂的布线图，这表明存在一个普遍的原则。
