Pattern Formation and Organization of Epithelial Tissues

[摘要] Developmental biology is a study of how elaborate patterns, shapes, and functions emerge as an organism grows and develops its body plan. From the physics point of view this is very much a self-organization process. The genetic blueprint contained in the DNA does not explicitly encode shapes and patterns an animal ought to make as it develops from an embryo. Instead, the DNA encodes various proteins which, among other roles, specify how different cells function and interact with each other. Epithelial tissues, from which many organs are sculpted, serve as experimentally- and analytically-tractable systems to study patterning mechanisms in animal development. Despite extensive studies in the past decade, the mechanisms that shape epithelial tissues into functioning organs remain incompletely understood. This thesis summarizes various studies we have done on epithelial organization and patterning, both in abstract theory and in close contact with experiments. A novel mechanism to establish cellular left-right asymmetry based on planar polarity instabilities is discussed. Tissue chirality is often assumed to originate from handedness of biological molecules. Here we propose an alternative where it results from spontaneous symmetry breaking of planar polarity mechanisms. We show that planar cell polarity (PCP), a class of well-studied mechanisms that allows epithelia to spontaneously break rotational symmetry, is also generically capable of spontaneously breaking reflection symmetry. Our results provide a clear interpretation of many mutant phenotypes, especially those that result in incomplete inversion.To bridge theory and experiments, we develop quantitative methods to analyze fluorescence microscopy images. Included in this thesis are algorithms to selectively project intensities from a surface in z-stack images, analysis of cells forming short chain fragments, analysis of thick fluorescent bands using steerable ridge detector, and analysis of cell recoil in laser ablation experiments. These techniques, though developed in the context of zebrafish retina mosaic, are general and can be adapted to other systems. Finally we explore correlated noise in morphogenesis of fly pupa notum. Here we report unexpected correlation of noise in cell movements between left and right halves of developing notum, suggesting that feedback or other mechanisms might be present to counteract stochastic noise and maintain left-right symmetry.

[发布机构] University of Michigan

[效力级别] Fluorescence microscopy image analysis

[关键词] Epithelial tissues organization and patterning;Fluorescence microscopy image analysis;Planar cell chirality;Noise in morphogenesis;Left-right asymmetry;Spontaneous chiral symmetry breaking;Physics;Science;Physics