Homeostatic maintenance and age-related functional decline in the Drosophila ear
Homeostatic maintenance and age-related functional decline in the Drosophila ear
复制标题
果蝇耳朵的稳态维持和与年龄相关的功能衰退
DOI：
10.1101/764670
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Keder A
中科院分区：
文献类型：
--
作者：
Keder A
听力损失（ARHL）是对未来人类福祉的威胁。导致终末期听力下降的多种因素已经被确定;但对ARHL -或听力崩溃前的稳态维持-缺乏统一的理解。我们在这里对果蝇触角耳朵的稳态和衰老进行了深入分析。我们表明果蝇就像人类一样，表现出ARHL。通过关注最终听力损失之前的动态稳定阶段，我们发现了一组进化上保守的稳态基因。转录因子Onecut（最接近的人类直系同源物：ONECUT 2、ONECUT 3）、Optix（SIX 3、SIX 6）、Worniu（SNAI 2）和Amos（ATOH 1、ATOH 7、ATOH 8、NEUROD 1）成为关键调节因子，作用于果蝇听觉传导和放大分子机制核心成分的上游。在果蝇的听觉神经元中对稳态调节器的成人特异性操纵加速了-或保护了- ARHL。
Age-related hearing loss (ARHL) is a threat to future human wellbeing. Multiple factors contributing to the terminal auditory decline have been identified; but a unified understanding of ARHL - or the homeostatic maintenance of hearing before its breakdown - is missing. We here present an in-depth analysis of homeostasis and ageing in the antennal ears of the fruit flyDrosophila melanogaster. We show thatDrosophila, just like humans, display ARHL. By focusing on the phase of dynamic stability prior to the eventual hearing loss we discovered a set of evolutionarily conserved homeostasis genes. The transcription factors Onecut (closest human orthologues: ONECUT2, ONECUT3), Optix (SIX3, SIX6), Worniu (SNAI2) and Amos (ATOH1, ATOH7, ATOH8, NEUROD1) emerged as key regulators, acting upstream of core components of the fly’s molecular machinery for auditory transduction and amplification. Adult-specific manipulation of homeostatic regulators in the fly’s auditory neurons accelerated - or protected against - ARHL.
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