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

哺乳动物的色素细胞对听觉和视觉是必不可少的。尽管如此，人们对这些感觉背后的分子机制知之甚少。本研究的目的是阐明特别是卷黑素细胞从神经嵴发展。黑素细胞从神经管迁移到皮肤（毛囊和真皮）、眼睛（脉络膜）和内耳（血管纹）等。众所周知，RPE细胞对视觉功能至关重要。该功能的失败导致视网膜变性、视觉功能丧失，导致失明，而对于脉络膜中的黑素细胞卷，仅报道具有保护脉络膜血管免受光毒性的功能。作为我们研究的第一阶段，我们分析了两个突变株（Mitf^<mi-bw>/Mitf^<mi-bw>和Kit^<W-v>/Kit^W）的视网膜电图（ERG），这两个突变株都显示了由黑素细胞发育失败引起的黑眼白色（外套）表型。我们记录了这两个突变小鼠品系的ERG，并与正常小鼠的ERG进行比较，以确定没有神经嵴源性黑素细胞的小鼠是否具有正常的视觉功能。我们发现，这两个黑素细胞较少的突变体显示出增加的振荡电位（OP）。这一结果首次表明，黑色素细胞较少的小鼠可能具有异常的视觉感官。另一方面，我们在内耳中发现了一种新的基因表达，强烈表明内耳黑素细胞作为压力缓解剂的作用。该基因是谷胱甘肽S-转移酶α 4（Gsta 4）。Gsta 4编码参与许多组织的解毒过程的细胞溶质谷胱甘肽S-转移酶（GST）之一。对这些研究的功能分析在将来阐明色素细胞参与视听感觉方面应该是非常重要的。

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.