Wang Jingjing, O'Sullivan Matthew L, Mukherjee Dibyendu, Puñal Vanessa M, Farsiu Sina, Kay Jeremy N
Department of Neurobiology, Duke University School of Medicine, Durham, NC, 27710.
Program in Cell and Molecular Biology, Duke University School of Medicine, Durham, NC, 27710.
J Comp Neurol. 2017 Jun 1;525(8):1759-1777. doi: 10.1002/cne.24153. Epub 2017 Mar 7.
Müller glia, the most abundant glia of vertebrate retina, have an elaborate morphology characterized by a vertical stalk that spans the retina and branches in each retinal layer. Müller glia play diverse, critical roles in retinal homeostasis, which are presumably enabled by their complex anatomy. However, much remains unknown, particularly in mouse, about the anatomical arrangement of Müller cells and their arbors, and how these features arise in development. Here we use membrane-targeted fluorescent proteins to reveal the fine structure of mouse Müller arbors. We find sublayer-specific arbor specializations within the inner plexiform layer (IPL) that occur consistently at defined laminar locations. We then characterize Müller glia spatial patterning, revealing how individual cells collaborate to form a pan-retinal network. Müller cells, unlike neurons, are spread across the retina with homogenous density, and their arbor sizes change little with eccentricity. Using Brainbow methods to label neighboring cells in different colors, we find that Müller glia tile retinal space with minimal overlap. The shape of their arbors is irregular but nonrandom, suggesting that local interactions between neighboring cells determine their territories. Finally, we identify a developmental window at postnatal Days 6 to 9 when Müller arbors first colonize the synaptic layers beginning in stereotyped inner plexiform layer sublaminae. Together, our study defines the anatomical arrangement of mouse Müller glia and their network in the radial and tangential planes of the retina, in development and adulthood. The local precision of Müller glia organization suggests that their morphology is sculpted by specific cell to cell interactions with neurons and each other.
穆勒胶质细胞是脊椎动物视网膜中数量最多的胶质细胞，具有复杂的形态，其特征是有一个垂直的茎干贯穿视网膜并在每个视网膜层分支。穆勒胶质细胞在视网膜内环境稳定中发挥着多种关键作用，推测这是由其复杂的解剖结构所促成的。然而，关于穆勒细胞及其树突的解剖结构，以及这些特征在发育过程中是如何形成的，仍有许多未知之处，尤其是在小鼠中。在这里，我们使用膜靶向荧光蛋白来揭示小鼠穆勒树突的精细结构。我们发现在内网状层（IPL）内存在亚层特异性的树突特化，这些特化始终出现在特定的层状位置。然后，我们对穆勒胶质细胞的空间模式进行了表征，揭示了单个细胞如何协作形成一个全视网膜网络。与神经元不同，穆勒细胞以均匀的密度分布在整个视网膜上，并且它们的树突大小随离心率变化不大。使用脑彩虹方法以不同颜色标记相邻细胞，我们发现穆勒胶质细胞以最小的重叠覆盖视网膜空间。它们树突的形状不规则但并非随机，这表明相邻细胞之间的局部相互作用决定了它们的区域。最后，我们确定了一个出生后第6至9天的发育窗口，此时穆勒树突开始从定型的内网状层亚层开始首次定殖于突触层。总之，我们的研究定义了小鼠穆勒胶质细胞及其网络在视网膜径向和切向平面上在发育和成年期的解剖结构。穆勒胶质细胞组织的局部精确性表明，它们的形态是由与神经元以及彼此之间特定的细胞间相互作用塑造的。
