Department of Otorhinolaryngology, Head and Neck Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Neurosci Lett. 2018 Jan 1;662:185-188. doi: 10.1016/j.neulet.2017.10.030. Epub 2017 Oct 18.
The eyes absent (EYA)-like genes are essential for the formation of sensory organs among fly (Drosophila melanogaster) and mammals. EYA4, one of the vertebrate genes of Eya family, is reported to be causative for late-onset mid-frequency sensorineural hearing loss in humans, while Eya4-deficient mice exhibited congenital profound deafness and otitis media with effusion due to the eustachian tube dysmorphology. Because of the species difference in the phenotype, the pathophysiology of EYA4 in the human cochlea has yet to be elucidated. Here, we examine the expression pattern of EYA4 in the cochlea of common marmoset (Callithrix jacchus), a non-human primate. The results indicated a distinct expression pattern of EYA4 in the adult marmoset cochleae, especially strong in all supporting cells, while in mouse their expressions were diminished. Interestingly, EYA4 expression in the hair cells, supporting cells and neurons was co-localized with sine oculis homeobox-SIX1, a transcription factor essential for the transcriptional activity of EYA4. The results revealed inter-species differences in the expression pattern of EYA4 gene in supporting cells between primates and rodents. The results also indicated a fundamental role of EYA4 in the primate auditory cells. Experiments with primate models such as marmosets or with human cochlear cells may provide cues about the unknown pathogenesis of EYA4-related hearing loss.
EYA-样基因对于果蝇(Drosophila melanogaster)和哺乳动物感觉器官的形成至关重要。EYA4 是 Eya 家族的脊椎动物基因之一,据报道,它是导致人类迟发性中频感音神经性听力损失的原因,而 Eya4 缺失的小鼠由于咽鼓管畸形而表现出先天性重度耳聋和中耳积液。由于表型的物种差异,EYA4 在人类耳蜗中的病理生理学尚未阐明。在这里,我们研究了 EYA4 在普通狨猴(Callithrix jacchus)耳蜗中的表达模式,普通狨猴是一种非人类灵长类动物。结果表明,EYA4 在成年狨猴耳蜗中的表达模式明显不同,尤其是在所有支持细胞中表达强烈,而在小鼠中表达减弱。有趣的是,毛细胞、支持细胞和神经元中的 EYA4 表达与 sine oculis homeobox-SIX1 共定位,后者是 EYA4 转录活性所必需的转录因子。这些结果揭示了 EYA4 基因在灵长类和啮齿动物支持细胞中的表达模式存在种间差异。结果还表明 EYA4 在灵长类听觉细胞中具有基本作用。使用狨猴等灵长类动物模型或人类耳蜗细胞进行实验,可能会为 EYA4 相关听力损失的未知发病机制提供线索。