Uncovering molecular mechanism of inner ear/lateral line hair cells functioning and development is the aim of this study. It will be among the first efforts to systematically screen through the zebrafish mutants generated by an insertional mutagenesis screen that is near completion in the Dr. Nancy Hopkins laboratory. This screen has identified over 500 genes which, when mutated, disrupts early development. Some of these genes have been identified as having a role in different part of nervous system development. These mutants will provide a fertile ground for identification of genes that participate the function and development of hair ceils.
My first aim i s to further characterize the pinball wizard (pwi) mutant, which have specific defects on mechanotransduction of hair cells. With the collaboration with Dr. David Corey's laboratory, electrophysiological analysis as well as morphological analysis at EM level will be used to gain further insight into the role of novel protein Pinball wizard (Pwi) in mechanotransduction. Second, I will screen through all of the mutants to identify those with a defect in styryl dye, FM 1-43, uptake. The Uptake of FM 1-43 has been shown to be pass directly through mechanotransduction channels at the tips of hair cell stereocilia. The mutants identified will either have impaired mechanotransduction, or have defects in hair cell development- They will be subject to further analysis, including a description of the mutant, the expression pattern of the gene during wild-type development.
| Lin, Shuh-Yow; Vollrath, Melissa A; Mangosing, Sara et al. (2016) The zebrafish pinball wizard gene encodes WRB, a tail-anchored-protein receptor essential for inner-ear hair cells and retinal photoreceptors. J Physiol 594:895-914 |
| Lin, Shuh-Yow; Corey, David P (2005) TRP channels in mechanosensation. Curr Opin Neurobiol 15:350-7 |
