Wang F, Eagleson K L, Levitt P
Neuroscience Graduate Program, University of Southern California, Los Angeles, CA.
Department of Pediatrics, The Saban Research Institute, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, CA.
Brain Res. 2015 Aug 7;1616:157-165. doi: 10.1016/j.brainres.2015.05.005. Epub 2015 May 11.
Synapse formation is a critical process during neural development and is coordinated by multiple signals. Several lines of evidence implicate the Plexin-D1 receptor in synaptogenesis. Studies have shown that Plexin-D1 signaling is involved in synaptic specificity and synapse formation in spinal cord and striatum. Expression of Plexin-D1 and its principal neural ligand, Sema3E, by neocortical neurons is temporally and spatially regulated, reaching the highest level at the time of synaptogenesis in mice. In this study, we examined the function of Plexin-D1 in synapse formation by primary neocortical neurons in vitro. A novel, automated image analysis method was developed to quantitate synapse formation under baseline conditions and with manipulation of Plexin-D1 levels. shRNA and overexpression manipulations caused opposite changes, with reduction resulting in less synapse formation, an effect distinct from that reported in the striatum. The data indicate that Plexin-D1 operates in a cell context-specific fashion, mediating different synaptogenic outcomes depending upon neuron type.
突触形成是神经发育过程中的一个关键过程，由多种信号协调。多条证据表明，丛状蛋白-D1受体参与突触形成。研究表明，丛状蛋白-D1信号传导参与脊髓和纹状体的突触特异性和突触形成。新皮层神经元中丛状蛋白-D1及其主要神经配体Sema3E的表达在时间和空间上受到调控，在小鼠突触形成时达到最高水平。在本研究中，我们在体外研究了原代新皮层神经元中丛状蛋白-D1在突触形成中的功能。我们开发了一种新颖的自动图像分析方法，以在基线条件下和操纵丛状蛋白-D1水平的情况下定量突触形成。短发夹RNA（shRNA）和过表达操作引起相反的变化，减少会导致突触形成减少，这一效应与纹状体中报道的不同。数据表明，丛状蛋白-D1以细胞背景特异性方式发挥作用，根据神经元类型介导不同的突触形成结果。
