Genetic analysis of the function and development of pigment cells essential for visual and auditory senses

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Mammalian pigment cells are essential for audio-visual senses. Still, little is known about the molecular mechanisms underlying these senses. The aim of this study is to elucidate especially the rolls of melanocytes developed from the neural crest. Melanocytes migrate from the neural tube to the skin (hair follicle and dermis), eye (choroid) and inner ear (stria vascularis) and so on. The choroid is adjacent to the RPE surrounding the eye. It is well known that RPE cells are essential for visual function. A failure of this function leads to degeneration of the retina, loss of visual function, resulting in blindness, while for the rolls of melanocytes in choroid, it was only reported to have function to protect choroidal blood vessels from light toxicity. As the first stage of our research, we analyzed the electroretinogram (ERG) of two mutant strains (Mitf^<mi-bw>/Mitf^<mi-bw> and Kit^<W-v>/Kit^W), both showing the black-eyed white (coat) phenotype caused by failure of melanocyte development. We recorded the ERGs of these two mutant mouse strains and compared with the normal mouse ERG to ascertain whether mice without neural crest-derived melanocytes have normal visual function or not. We found that both melanocyte-less mutants show increased oscillatory potentials (OPs). This result first suggests that melanocyte-less mice may have abnormal visual senses. On the other hand, we found a new gene expression in the inner ear strongly suggesting a role of inner ear melanocytes as a stress reliever. The gene is glutathioneS-transferase alpha 4 (Gsta4). Gsta4 encodes one of the cytosolic glutathione S-transferases (GSTs) participating in detoxification processes of many tissues. Functional analysis of these lines of researches should be very important in future to elucidate the involvement of pigment cells in the audio-visual senses.