The canonical Wnt signaling pathway affects regeneration of mechanosensory hair cells in Danio Rerio
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In vertebrates, mechanosensory hair cells are located in the inner ear and mediate hearing. When damage to these specialized cells occur, it leads to irreversible hearing loss. Not only do aquatic vertebrates have inner ear hair cells, but mechanosensory hair cells are also found in the lateral line system. The lateral line system senses variation in water current. Neuromast mechanosensory organs comprise the lateral line and consist of hair cells, supporting cells and mantle cells. In zebrafish, hair cells of the lateral line have demonstrated a robust ability to regenerate following damage. Previous studies have suggested that hair cells are replaced via the division and differentiation of their surrounding support cells. Research using pharmacological modulators of the Wnt pathway has suggested that the Wnt pathway potentially plays a role in lateral line hair cell regeneration. In this current study, we examine the role of the Wnt signaling pathway in hair cell regeneration by employing Wnt pathway mutant zebrafish lines. Mutations in LRP5, Lef1 and a negative regulator of Wnt signaling, Kremen1, were used to study the role of Wnt signaling in regeneration of lateral line hair cells in zebrafish. These Wnt pathway mutant lines show no change in proliferation of supporting cells post injury and shifts in the number of regenerated hair cells. The results obtained in this study suggest that disrupting Wnt signaling at distinct points along the pathway leads to differential patterns of hair cell regeneration, including specification of dividing support cells. Understanding the role of the Wnt signaling pathway in zebrafish mutants will contribute to subsequent studies on hearing loss reversal in mammals with inner ear hair cell damage.
Table of Contents
Introduction -- Materials and methods -- Results -- Discussion
M.S. (Master of Science)