Probing the elusive molecular mechanisms underlying vertebrate planar cell polarity

点击翻译按钮获取中文摘要

During vertebrate embryonic development, an unassuming ball of cells rapidly proliferates, grows, and is actively re-modeled into a recognizable ‘adult' body plan. This remarkable transformation involves countless changes in cell shape, pattern and movement, (collectively referred to as “cell polarity”), which ultimately assemble complex structures like organs, faces and limbs. Slight changes to any of these events can dramatically alter normal form and organ function.******In the following proposal, we use an elegant experimental model system – the zebrafish – to understand how cell polarity is controlled at a molecular and genetic level, over the course of embryonic development. Zebrafish embryogenesis is remarkably similar to that of mammals. However, zebrafish embryos are abundant, transparent, easily grown under a microscope, and we have established powerful techniques to actually image (in real time) the microscopic changes in cell structure and movement that occur throughout development. Furthermore, zebrafish are well suited for genetic studies, and we can selectively and systematically manipulate gene function, at different points in space and time, to study their effects on developmental processes. ******Here, we employ cell biology, embryology, and classic genetic approaches in zebrafish to determine how cell polarity is intricately controlled during embryonic patterning and morphogenesis. Proposed research holds tremendous potential to expand our understanding of organ development, and to identify novel molecular and cell biological mechanisms that co-ordinate extrinsic patterning cues with cell structure and movement over the course of complex developmental events that shape the vertebrate embryo.