Data from: An extracellular biochemical screen reveals that FLRTs and Unc5s mediate neuronal subtype recognition in the retina

In the inner plexiform layer of the mouse retina, ~70 neuronal subtypes form a stereotyped circuit that underlies visual processing. During development, subtypes organize into an intricate laminar structure. This organization is choreographed by extracellular interactions that mediate cell recognition events. To identify recognition proteins involved in lamination, we utilized microarray data from 13 subtypes to identify differentially-expressed cell surface and secreted proteins. Using these candidates, we performed a biochemical screen and identified ~50 previously-unknown receptor-ligand pairs. We tested the response of retinal neurons to several candidates and found that both members of one interaction pair, FLRT2-Unc5C, induce repulsion; each in a different neuronal subtype(s). Consistent with a repulsive role in mediating lamination, we observed a complementary expression pattern of FLRT2 and Unc5C in vivo. We identified that Starburst amacrine cells express FLRT2 and are repelled by Unc5C. These data support a repulsive mechanism for laminar restriction of Starburst amacrines.

在小鼠视网膜内丛状层中，约70种神经元亚型构成一套定型化的神经环路，该环路支撑视觉处理过程。发育过程中，这些神经元亚型会组装为复杂的层状结构，这一构建过程由介导细胞识别事件的细胞外相互作用所调控。为鉴定参与层状构建的识别蛋白，我们利用13种神经元亚型的微阵列（microarray）数据，筛选出差异表达的细胞表面蛋白与分泌蛋白。基于这些候选蛋白，我们开展了生化筛选，最终鉴定出约50种此前未被发现的受体-配体（receptor-ligand）对。我们检测了视网膜神经元对多种候选蛋白的响应，发现其中一对相互作用蛋白FLRT2与Unc5C的两个成员均可诱导排斥反应，且分别作用于不同的神经元亚型。与二者在介导层状构建中发挥排斥作用的结论一致，我们在体内观察到FLRT2与Unc5C的表达模式呈互补分布。我们鉴定出星爆无长突细胞（Starburst amacrine cells）表达FLRT2，且会被Unc5C诱导排斥。上述数据支持星爆无长突细胞的层状限制性定位依赖排斥机制这一结论。