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Damage to the mechanosensory hair cells of the inner ear results in hearing loss and balance impairment. Although hair cell loss is permanent in humans and other mammals, nonmammalian vertebrates such as zebrafish (Danio rerio) can regenerate fully functional hair cells, making them a useful model for studying the molecular mechanisms underlying hair cell regeneration. In zebrafish, hair cells are organized into sensory organs called neuromasts. Previous studies have reported the downregulation of fat2 in the mantle cells, a type of support cell located in the neuromast that gives rise to hair cells following hair cell death. The Fat family of cadherins are involved in planar cell polarity (PCP) and regulation of cell proliferation, both of which are important for development and regeneration. In this study, I investigated Fat2’s function in hair cell development and planar cell polarity through the use of immunohistochemical assays and morpholino oligonucleotide (MO)-mediated knockdown of fat2. Immunofluorescent labeling of zebrafish larvae with an antibody against Fat2 confirms that this protein localizes in the mantle cells. Although there does not appear to be a difference in the PCP of the neuromasts of MO-injected (morphant) larvae and sham-injected control larvae, Fat2 affects the hair cell populations of these two groups. Over time, the neuromasts of morphant larvae have significantly fewer hair cells than control larvae, indicating slowed cell division in morphants. These results suggest that Fat2 plays a role in cell division during development as a possible factor involved in determining the rate of mantle cell proliferation.
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Palfini, Victoria Leigh, "The role of cadherin Fat2 in zebrafish hair cell development and planar cell polarity" (2017). Senior Projects Spring 2017. 113.