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

The orderly packing and precise arrangement of individual epithelial cells is essential to the functioning of many biological tissues, including sensory structures in animals such as photoreceptors in the retina of the eye and hair cells in the auditory epithelium of the inner ear. Various biological and physical influences can affect epithelial cell geometry, among them cell-cell adhesion, cytoskeletal dynamics, and macroscopic mechanical stress, but the changes in cell shape and position that generate planar geometric ordering are still only partially understood. Ultimately, quantitative physical models will be needed to unravel the dynamic regulatory behavior responsible for the regular arrays of cells seen in many biological systems. The proposed research will be accomplished by an interdisciplinary team that relies on ideas and techniques from both statistical physics and developmental biology. The goal is to generate mathematical models that can be tested directly with biological experiments, and with these models to discover mechanisms that position cone photoreceptors in a precise array in the zebrafish retina. The computational models developed in this project will be the first to explore how differences in cell-cell affinities combined with directed mechanical stresses can generate longer-ranged order in an epithelium. These studies will also provide a unique understanding of the biological and physical mechanisms underlying the planar organization of vertebrate photoreceptors in the developing eye. A research team diverse in gender, ethnicity, and scientific discipline will be built through continuing involvement of the PI, Co-PI and postdoctoral researcher in campus-based and external programs to promote diversity of undergraduate and graduate science students. A course module on biological modeling will be developed for graduate students, and new computational tools for understanding the emergence of biological form will be made freely available.