A major question in biology is that of embryonic development: how a single cell generates all of the body’s diverse tissues and organs. During this process, cells must make decisions about fate – what tissue or organ to become. But a crucial component of this question is how cells are organized into the precise, stereotyped tissue structures that are essential for proper organ function – the process of developmental tissue morphogenesis. Disruptions to morphogenesis commonly result in organ dysfunction. Despite dramatic advances in our molecular understanding of how cells make fate decisions, the cellular and molecular mechanisms underlying tissue morphogenesis are still poorly understood: our best potential for studying such dynamic processes requires multidimensional imaging of embryonic events in vivo and computational approaches to extract, analyze, and visualize imaging data and results. This presents a number of obstacles, both in terms of imaging and analysis. Our goal is to understand tissue morphogenesis by imaging whole organ development in a living organism (live and in real time). We circumvent barriers to optical accessibility by using zebrafish embryos (Danio rerio) as our model system, which develop externally to the mother and, importantly, are optically transparent. This facilitates 4-dimensional (3-dimensional volume over time) in vivo imaging of morphogenetic events using simple genetically encoded fluorescent proteins. To extract, analyze, and visualize imaging data, we developed a computational toolkit for 4-dimensional cell tracking and visualization. These programs allow us to determine precisely when and where cells move within the embryo as organs are forming. Using multidimensional imaging of zebrafish and this toolkit, we are determining how the vertebrate eye forms. Our recent work is focused on how a specific part of the eye, the choroid fissure, forms: disruptions to choroid fissure morphogenesis result in a birth defect of visual impairment, uveal coloboma. We have determined the cellular mechanisms underlying normal choroid fissure formation, as well as how it is disrupted in a zebrafish model of human uveal coloboma.

Multidimensional imaging and computational approaches to understanding tissue morphogenesis

251st National Meeting (2016)

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