Center for Neurobiology Research, Fralin Biomedical Research Institute at Virginia Tech Carilion, Roanoke, VA 24016.
Graduate Program in Translational Biology, Medicine, and Health, Virginia Tech, Blacksburg, VA 24061.
Proc Natl Acad Sci U S A. 2021 Oct 19;118(42). doi: 10.1073/pnas.2104343118.
Information about features in the visual world is parsed by circuits in the retina and is then transmitted to the brain by distinct subtypes of retinal ganglion cells (RGCs). Axons from RGC subtypes are stratified in retinorecipient brain nuclei, such as the superior colliculus (SC), to provide a segregated relay of parallel and feature-specific visual streams. Here, we sought to identify the molecular mechanisms that direct the stereotyped laminar targeting of these axons. We focused on ipsilateral-projecting subtypes of RGCs (ipsiRGCs) whose axons target a deep SC sublamina. We identified an extracellular glycoprotein, Nephronectin (NPNT), whose expression is restricted to this ipsiRGC-targeted sublamina. SC-derived NPNT and integrin receptors expressed by ipsiRGCs are both required for the targeting of ipsiRGC axons to the deep sublamina of SC. Thus, a cell-extracellular matrix (ECM) recognition mechanism specifies precise laminar targeting of ipsiRGC axons and the assembly of eye-specific parallel visual pathways.
关于视觉世界特征的信息由视网膜中的电路进行解析，然后由不同亚型的视网膜神经节细胞 (RGC) 将其传输到大脑。来自 RGC 亚型的轴突在视网膜靶脑核（如上丘）中分层，为平行和特征特定的视觉流提供分离的中继。在这里，我们试图确定指导这些轴突刻板分层靶向的分子机制。我们专注于其轴突靶向 SC 深亚层的同侧投射 RGC 亚型（ipsiRGCs）。我们鉴定出一种细胞外糖蛋白 Nephrontin (NPNT)，其表达仅限于该 ipsiRGC 靶向的亚层。SC 衍生的 NPNT 和由 ipsiRGC 表达的整联蛋白受体对于 ipsiRGC 轴突靶向 SC 的深亚层都是必需的。因此，细胞-细胞外基质 (ECM) 识别机制指定了 ipsiRGC 轴突的精确分层靶向以及眼特异性平行视觉通路的组装。
