Understanding prosensory specification for improved regenerative therapies in the inner ear

我们的听觉和平衡感依赖于位于内耳感觉器官中的特殊“毛”细胞。毛细胞只在内耳的胚胎发育过程中产生，它们在成年后的消失是听力损失的主要原因，特别是在老龄化人口中。听力损失的治疗仅限于助听器或人工耳蜗植入，并且对于新的和更有效的治疗方法存在相当大的需求和压力。一种可能的治疗方法是诱导受损内耳的毛细胞再生--这一过程在非哺乳类脊椎动物中自然发生。目前实现这一目标的方法依赖于人工重新激活“原毛细胞”信号，负责在胚胎发育期间诱导毛细胞形成。然而，越来越多的证据表明，当暴露于这些信号时，成年耳蜗的细胞不能容易地转化为毛细胞。另一种策略可能是将成人内耳的细胞转化为“前感觉”细胞，在正常发育过程中，这些细胞是产生毛细胞及其相关“支持”细胞的母细胞。实现这一目标的第一步是了解这些前感觉细胞在正常发育过程中是如何形成的。使用DNA测序和生物信息学方法，我们已经确定了一些基因和信号，可能是重要的前感觉细胞的形成。本项目的目的是通过人工修饰它们在鸡胚内耳发育过程中的表达或活性来测试它们的功能。这个项目的结果将帮助我们确定特定的基因和细胞间的通讯系统，这些系统可以被操纵来触发受损内耳的毛细胞再生。在未来，这项研究可以为人类听力损失的更有效治疗开辟新的途径。

Our senses of hearing and balance depend on specialized 'hair' cells located in the sensory organs of the inner ear. The hair cells are only produced during the embryonic development of the inner ear, and their disappearance in adult life is the leading cause of hearing loss, in particular in the ageing population. The treatments for hearing loss are limited to hearing aids or cochlear implants, and there is considerable need and pressure for new and more efficient therapies. One possible cure could be to induce hair cell regeneration in the damaged inner ear - a process that is naturally occurring in non-mammalian vertebrates. The current approaches to achieve this rely on the artificial re-activation of 'pro-hair cell' signals, responsible for the induction of hair cell formation during embryonic development. However, growing evidence indicate that the cells of the adult cochlea cannot easily convert into hair cells when exposed to those signals. An alternative strategy might be to turn cells of the adult inner ear into 'prosensory' cells, which during normal development are the parent cells giving rise to both hair cells and their associated 'supporting' cells. A first step towards this goal is to understand how these prosensory cells are formed during normal development. Using DNA-Sequencing and bioinformatics methods, we have already identified a number of genes and signals that could be potentially be important for the formation of prosensory cells. The aims of this project are to test their functions, by artificially modifying their expression or activity during the development of the embryonic chicken inner ear. The results of this project will help us to pinpoint the specific genes and cell-to-cell communication systems that could be manipulated to trigger hair cell regeneration in the damaged inner ear. In the future, this research could open up new venues for more efficient therapies for hearing loss in humans.