Davies, Alexander Lloyd; (2002) Role of the frizzled signalling pathway in control of hair cell production and polarity in the developing inner ear. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The sensory patches of the inner ear consist of two types of cell: sensory hair cells and supporting cells. The pattern is such that supporting cells surround each hair cell and no two hair cells touch each other. Hair cells also possess planar cell polarity; their stereociliary bundles are precisely oriented in the plane of the epithelium. How hair cells are determined and then oriented is unknown. The mechanosensory bristles of the fruit fly Drosophila melanogaster can be thought of as structures analogous to the sensory patches of vertebrate inner ears. Genetic analysis has shown that several intercellular signalling pathways are required for bristle formation, including those mediated by Notch and Frizzled receptors, and Notch signalling appears to have an analogous function in ear development. I have explored the possibility that homologues of Frizzled signalling pathway genes may be involved in hair cell production and polarity in the inner ear. I have shown, by in situ hybridization, that several Frizzled pathway genes are expressed in the developing sensory patches of the chick embryonic ear concomitant with hair cell birth and differentiation and, subsequently, become restricted to the hair cell or supporting cell subpopulation. Further, I have used retroviral vectors to misexpress full-length chick frizzled-1, chick frizzled-7 and human dishevelled-1, as well as various truncated (dominant-negative) Dishevelled-1 constructs. The results obtained suggest that a more complex situation may exist in vertebrates than in the fruit fly, and that the Frizzled signalling pathway may have numerous roles in inner ear development.

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