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

Regents Of The University Of Michigan - Ann Arbor, Ann Arbor MI

Investigators

Abstract

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.