Role of the centrosome in vertebrate development

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The centrosome is a cellular organelle that consists of two barrel-shaped centrioles and the proteins that closely surround them. It has an important role in cell division, but a less clear role in cellular differentiation and function. It has become increasingly apparent that the centrosome is adapted to form apart of the cilium. Cilia may have a number of roles in vertebrate development and some are defective in certain inherited diseases of human development. This project will investigate the role of the centrosomal proteins in vertebrate development. We expect centrosome proteins to form important parts of the modified cilia of sensory neurons which house light, sound and smell receptors. We also expect the centrosome to have an important role in neurogenesis, in defining the number and types of cells in the layers of the brain and eye. We will find the centrosome proteins that are important in such structures and processes by systematically depleting the known inventory of centrosome proteins from zebrafish embryos then monitoring the effect on embryogenesis, neurogenesis and cilia formation. We will study the histology of these embryos to determine how the structure of the tissues and organs are affected when centrosome proteins are absent. Immunofluorescence analysis of whole and sectionned embryos and two-photon confocal time-lapse microscopy will be used to monitor how cellular behaviour and subcellular structure is altered. We will then find interacting proteins to further define the molecular components of these processes and in this way seek to place these centrosome proteins, many of whose function remains quite mysterious, in the wider context of other developmental pathways.