The Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Neuron. 2011 Aug 11;71(3):460-73. doi: 10.1016/j.neuron.2011.06.009.
In the vertebrate retina, neurites from distinct neuronal cell types are constrained within the plexiform layers, allowing for establishment of retinal lamination. However, the mechanisms by which retinal neurites are segregated within the inner or outer plexiform layers are not known. We find that the transmembrane semaphorins Sema5A and Sema5B constrain neurites from multiple retinal neuron subtypes within the inner plexiform layer (IPL). In Sema5A⁻/⁻; Sema5B⁻/⁻ mice, retinal ganglion cells (RGCs) and amacrine and bipolar cells exhibit severe defects leading to neurite mistargeting into the outer portions of the retina. These targeting abnormalities are more prominent in the outer (OFF) layers of the IPL and result in functional defects in select RGC response properties. Sema5A and Sema5B inhibit retinal neurite outgrowth through PlexinA1 and PlexinA3 receptors both in vitro and in vivo. These findings define a set of ligands and receptors required for the establishment of inner retinal lamination and function.
在脊椎动物的视网膜中，来自不同神经元细胞类型的神经突被限制在神经丛层内，从而建立视网膜的分层。然而，视网膜神经突在内丛状层或外丛状层中被分隔的机制尚不清楚。我们发现，跨膜信号素 Sema5A 和 Sema5B 将来自多种视网膜神经元亚型的神经突限制在内丛状层（IPL）内。在 Sema5A⁻/⁻; Sema5B⁻/⁻ 小鼠中，视网膜神经节细胞（RGCs）和无长突细胞和双极细胞表现出严重的缺陷，导致神经突错误靶向到视网膜的外部分。这些靶向异常在外丛状层（OFF）中更为明显，导致特定 RGC 反应特性的功能缺陷。Sema5A 和 Sema5B 通过 PlexinA1 和 PlexinA3 受体在体外和体内均抑制视网膜神经突的生长。这些发现定义了一组配体和受体，它们是建立内视网膜分层和功能所必需的。
