Emergence of Geometric Order and Cell Identity in the Cone Photoreceptor Mosaic

动物的生命始于一个非凡的自我组织过程：从一个微小的单细胞卵子开始，它们发展成为一个令人难以置信的复杂有机体。此外，他们这样做没有集中控制。没有主建造者将每个细胞引导到最终身体计划的正确位置。活细胞究竟是如何协同创造出精确构造的组织和器官的，这是发育生物学的核心问题。这个项目将研究鱼眼中这种自组织的一个特殊例子。它将使用多种方法，包括对眼睛组织的观察、激光脉冲对眼睛组织的扰动和计算机模拟。这些技术将提供对鱼眼系统更深入的了解。这种关于生物自组织的基本知识具有潜在的应用范围，从新的疾病治疗到受眼睛工作机制启发的合成自组织系统的设计。作为物理学家和生物学家之间的合作，该项目将为多层次的跨学科教育创造机会。调查人员将特别强调让来自传统上代表性不足的背景的学生在本科职业生涯的早期参与研究。该项目将结合生物实验和数学模型来研究斑马鱼视网膜中锥体感光细胞的惊人晶体排列。指导性假设是，这种有序晶格的形成取决于环韧带对视网膜上皮施加的各向异性机械应力，环韧带是包围视网膜边缘的一种刚性组织环。先前的研究表明，机械力和平面细胞极性之间相互作用的数学模型可以再现许多观察到的视锥细胞规则排列的特征，特别是，该模型正确地预测了受干扰视网膜中细胞之间强烈各向异性相互作用的存在。目前的项目将直接测试指导性假设。研究人员将使用在色素突变背景下产生的新的转基因菌株，对活的成年鱼的视网膜进行首次成像和激光显微手术。这将提供在空间和时间上马赛克顺序程度的细粒度定量表征。然后，研究人员将使用显微外科测量视网膜应力各向异性，观察环状韧带和光感受器细胞消融对这一顺序的影响。

Animals begin their life by undergoing a remarkable process of self-organization: Starting from a tiny, single-celled egg, they develop into an incredibly complex organism. Moreover, they do so without centralized control. No master builder directs each cell to its correct position in the final body plan. How exactly living cells are able to collaborate to create precisely constructed tissues and organs is the central question of developmental biology. This project will study a particular example of such self-organization in the fish eye. It will use a combination of approaches, including observations of eye organization, perturbation of this organization by laser pulses, and computer simulations. These techniques will provide a deeper understanding of the fish eye system. This fundamental knowledge about biological self-organization has potential applications ranging from new disease treatments to the design of synthetic self-organizing systems inspired by the mechanisms at work in the eye. As a collaboration between a physicist and a biologist, the project will create opportunities for interdisciplinary education at many levels. The investigators will place a special emphasis on involving students from traditionally underrepresented backgrounds in research early in their undergraduate careers.The project will combine biological experiments with mathematical modeling to study the emergence of the striking crystalline arrangement of cone photoreceptor cells in the zebrafish retina. The guiding hypothesis is that the formation of this ordered lattice depends on anisotropic mechanical stresses imposed on the retinal epithelium by the annular ligament, a rigid ring of tissue that surrounds the retinal margin. Prior work has shown that a mathematical model of the interaction between mechanical forces and planar cell polarity can reproduce many of the observed features of the regular arrangement of cones, and, in particular, the model correctly predicted the presence of strongly anisotropic interactions between cells in perturbed retina. The current project will test the guiding hypothesis directly. The investigators will use new transgenic strains generated on a pigment mutant background to perform the first imaging and laser microsurgery of retinas in living, adult fish. This will provide a fine-grained quantitative characterization of the degree of mosaic order in space and time. Then, the investigators will observe how this order is affected by ablation of the annular ligament and the photoreceptor cells, using microsurgery to measure stress anisotropy in the retina.