Establishment and maintenance of cell polarity and.. (TISSUE POLARITY)
Establishment and maintenance of cell polarity and tissue architecture in the lateral-line system of the zebrafish
Start date: Jul 1, 2008,
End date: Jun 30, 2010
The establishment and maintenance of cellular polarity are critical for organ function. In addition to the ubiquitous apicobasal axis, many epithelial cells display a second polarity axis within the plane of the tissue, referred to as planar cell polarity. The orientation of hair-cell stereocilia in the inner ear represents a striking example of planar polarity in vertebrates. Although many of the proteins involved in the interpretation of the polarising cues have been identified, the mechanistic bases of t heir activity are not known.The motivation of this project is to understand the molecular and cellular mechanisms that generate the precise architecture of a sensory epithelium, with an emphasis on planar cell polarity. Hair cells provide an excellent mod el for cell-polarity studies. Experiments will be done using the anatomically simple mechanosensory organs of the lateral line in the zebrafish, whose hair cells display a stereotyped planar polarity pattern. I will first investigate the cellular mechanism s that lead to the planar polarisation of hair cells during lateral-line development. Second, I will study how the polarised organisation is recovered after hair-cell regeneration.Preliminary evidence suggests that functional properties of progenitor cell s within the organ are determinants of hair-cell polarisation. I shall test this hypothesis by tracking protein localisation patterns during hair-cell development in vivo, in wild type and mutant specimens with randomised planar polarity. To facilitate the se analysis, I will use transgenic reporter lines with specific expression in the lateral line, in combination with fluorescently tagged proteins that distribute asymmetrically in hair cells. This innovative approach shall lead to a deeper understanding of the mechanisms governing the formation and repair of sensory organs in vertebrates, a process that I plan to explore further as an independent investigator.
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