BACKGROUND The multiplex, lattice mosaic of cone photoreceptors in the adult fish retina is a compelling example of a highly ordered epithelial cell pattern, with single cell width rows and columns of cones and precisely defined neighbor relationships among different cone types. Cellular mechanisms patterning this multiplex mosaic are not understood. Physical models can provide new insights into fundamental mechanisms of biological patterning. In earlier work, we developed a mathematical model of photoreceptor cell packing in the zebrafish retina, which predicted that anisotropic mechanical tension in the retinal epithelium orients planar polarized adhesive interfaces to align the columns as cone photoreceptors are generated at the retinal margin during post-embryonic growth. METHODS With cell-specific fluorescent reporters and in vivo imaging of the growing retinal margin in transparent juvenile zebrafish we provide the first view of how cell packing, spatial arrangement, and cell identity are coordinated to build the lattice mosaic. With targeted laser ablation we probed the tissue mechanics of the retinal epithelium. RESULTS Within the lattice mosaic, planar polarized Crumbs adhesion proteins pack cones into a single cell width column; between columns, N-cadherin-mediated adherens junctions stabilize Müller glial apical processes. The concentration of activated pMyosin II at these punctate adherens junctions suggests that these glial bands are under tension, forming a physical barrier between cone columns and contributing to mechanical stress anisotropies in the epithelial sheet. Unexpectedly, we discovered that the appearance of such parallel bands of Müller glial apical processes precedes the packing of cones into single cell width columns, hinting at a possible role for glia in the initial organization of the lattice mosaic. Targeted laser ablation of Müller glia directly demonstrates that these glial processes support anisotropic mechanical tension in the planar dimension of the retinal epithelium. CONCLUSIONS These findings uncovered a novel structural feature of Müller glia associated with alignment of photoreceptors into a lattice mosaic in the zebrafish retina. This is the first demonstration, to our knowledge, of planar, anisotropic mechanical forces mediated by glial cells.

中文翻译：

---

各向异性的Müller神经胶质支架支持斑马鱼视网膜中感光细胞的多重晶格镶嵌。

背景技术成年鱼视网膜中视锥细胞感光体的多重，晶格马赛克是高度有序的上皮细胞模式的令人信服的例子，其具有单细胞宽度的视锥细胞行和列以及不同视锥类型之间精确定义的邻居关系。尚不了解将这种多重镶嵌图案化的细胞机制。物理模型可以提供有关生物学模式基本机制的新见解。在较早的工作中，我们开发了斑马鱼视网膜中感光细胞堆积的数学模型，该模型预测视网膜上皮中的各向异性机械张力会定向平面极化的胶粘剂界面，以对齐柱，因为胚胎后胚胎在视网膜边缘产生了锥形感光体。生长。方法利用细胞特异性荧光报告分子和透明幼斑马鱼中视网膜边缘生长的体内成像，我们首次了解了如何协调细胞的堆积，空间排列和细胞身份以构建晶格镶嵌。通过靶向激光消融，我们探查了视网膜上皮的组织力学。结果在晶格镶嵌物中，平面极化的Crumbs粘附蛋白将视锥细胞包装到单个细胞宽度的柱子中。在柱之间，N-钙黏着蛋白介导的粘附连接稳定了Müller胶质细胞的根尖过程。这些点状粘附连接处的活化pMyosin II浓度表明这些神经胶质带处于张力下，在圆锥柱之间形成物理屏障，并有助于上皮片中的机械应力各向异性。不料，我们发现，Müller胶质细胞顶突的这种平行带的出现先于将视锥堆积成单个细胞宽度的圆柱，这暗示了胶质细胞在晶格镶嵌的初始组织中的可能作用。穆勒胶质细胞的靶向激光消融直接表明，这些神经胶质过程支持视网膜上皮平面尺寸的各向异性机械张力。结论这些发现揭示了Müller胶质细胞的新结构特征，该结构特征与光感受器在斑马鱼视网膜中排列成格子马赛克有关。据我们所知，这是由神经胶质细胞介导的平面各向异性机械力的首次证明。提示胶质细胞在晶格镶嵌的初始组织中可能发挥作用。穆勒胶质细胞的靶向激光消融直接表明，这些神经胶质过程支持视网膜上皮平面尺寸的各向异性机械张力。结论这些发现揭示了Müller胶质细胞的新结构特征，该结构特征与光感受器在斑马鱼视网膜中排列成格子马赛克有关。据我们所知，这是由神经胶质细胞介导的平面各向异性机械力的首次证明。提示胶质细胞在晶格镶嵌的初始组织中可能发挥作用。穆勒胶质细胞的靶向激光消融直接表明，这些神经胶质过程支持视网膜上皮平面尺寸的各向异性机械张力。结论这些发现揭示了Müller胶质细胞的新结构特征，该结构特征与光感受器在斑马鱼视网膜中排列成格子马赛克有关。据我们所知，这是由神经胶质细胞介导的平面各向异性机械力的首次证明。结论这些发现揭示了Müller胶质细胞的新结构特征，该结构特征与光感受器在斑马鱼视网膜中排列成格子马赛克有关。据我们所知，这是由神经胶质细胞介导的平面各向异性机械力的首次证明。结论这些发现揭示了Müller胶质细胞的新结构特征，该结构特征与光感受器在斑马鱼视网膜中排列成格子马赛克有关。据我们所知，这是由神经胶质细胞介导的平面各向异性机械力的首次证明。