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关于人类听力障碍的新突破来自一个不太可能的来源:斑马鱼

发布时间:2019-11-03 20:36:58  来源:好孕妈妈社区    采编:太子阁生殖专家  

  科学家们了解了决定耳内微小毛细胞生长模式的机制。

  对斑马鱼基因组成的研究为人类先天性听力障碍的病因提供了全新的见解。

  来自卡迪夫大学的科学家们组成了一个研究小组,他们已经确定了特定的基因是如何支配我们耳朵里的微小细胞——所谓的毛细胞——的模式的,这些细胞使我们能够听到并处理声音。

  遗传因素被认为是导致超过50%的先天性听力丧失的原因,其中许多是由于微小毛细胞的失调或损伤。

  这些毛细胞成千上万地存在于耳蜗内,它们根据音高或频率对不同的声音做出“调整”。这是由于一个被称为“平面极化”的集体属性,或者是微小毛发排列的方向。当声音进入耳朵时,这些毛发会把声音的振动转化为电信号,并传递给大脑,让我们能够识别它。

  科学家们以斑马鱼为代表,阐明了特定基因的变化如何改变细胞排列的协调方向。

  研究结果发表在《自然通讯》杂志上。

  斑马鱼的体毛细胞非常相似,位于所谓的侧线器官内,用来读取水中的压力差。重要的是,斑马鱼在受损时可以再生这些毛发,这为科学家提供了一个理想的实验平台,让他们了解什么时候可能会出现问题。

  此外,由于内耳的不可达性,研究人类毛细胞的排列是极具挑战性的。

  在他们的研究中,研究小组调查了两种信号通路——PCP和Wnt——的基因,这两种通路同时存在于人类和斑马鱼体内,已知它们会影响毛细胞协调方向的方式。

  通过系统地关闭斑马鱼的这些基因,研究小组能够研究这些基因对毛细胞方向的多重影响。

  这是利用卡迪夫大学开发的新的统计特征来实现的,这使得科学家能够测量将要产生的毛细胞模式的类型,例如高度排列成行,而不是排列成行,或者排列成圆形结构。

  结果表明,毛细胞形态的规律性不仅会被破坏,产生随机的毛细胞方向,而且基因的某些改变会导致毛细胞出现圆形或螺旋型。

  第一作者Joaquin Navajas Acedo是斯托尔斯医学研究所研究生院的学生。我们刚刚开始理解这个令人兴奋的过程背后的复杂监管机制,我们希望更多的人开始使用这个系统来解决这个问题。”

  来自卡迪夫大学数学学院的托马斯·伍利博士是这项研究的合著者,他说:“研究的重要结果是,我们更好地理解了是什么影响了毛细胞的方向性,同样地,也知道了人类可能会出现什么问题。”这些发现为我们解决先天性听力问题提供了新的方向。”

  这项研究包括来自卡迪夫大学、斯托尔斯医学研究所和弗雷德·哈钦森癌症研究中心的科学家。

  Joaquin Navajas Acedo、Matthew G. Voas、Richard Alexander、Thomas Woolley、Jay R. h、Hua Li、Cecilia Moens和Tatjana Piotrowski于2019年9月5日在《自然通讯》上发表的“PCP和Wnt通路成分在斑马鱼机械感觉毛细胞定向过程中相互作用”。
 

Scientists gain understanding of mechanisms that determine growth patterns of tiny hair cells within the ear.

A study of the genetic make-up of zebrafish has provided brand new insights into the cause of congenital hearing disorders in humans.

A team including scientists from Cardiff University has identified how specific genes can dictate the patterns of the tiny cells — so-called hair cells — within our ears that allow us to hear and process sounds.

Genetic factors are thought to cause more than 50 percent of all incidents of congenital hearing loss, with many attributed to the misalignment or damage of tiny hair cells.

These hair cells exist in their thousands within the cochlea and are ‘tuned’ to respond to different sounds based on pitch or frequency. This is due to a collective property called ‘planar polarization’, or the orientation in which the tiny hairs are laid out. When sound enters the ear, the hairs change the sound vibrations into an electrical signal that is sent to the brain, allowing us to recognize it.

Using zebrafish as a proxy, scientists have shed light on how changes to specific genes alter the coordinated direction that these cells are laid out.

The findings have been published in the journal Nature Communications.

Zebrafish have very similar hairs cells along their body, within the so-called lateral line organ, which they use to read pressure differences in water.  Critically, zebrafish can regenerate these hairs when they are damaged, providing scientists with an ideal testbed to understand when things may go wrong.

Moreover, due to the inaccessibility of the inner ear, studying the alignment of hair cells in humans is extremely challenging.

In their study, the team investigated the genes underlining two signaling pathways – PCP and Wnt – that are present in both humans and zebrafish and are known to affect the way in which hair cells coordinate their orientations.

By systematically switching these genes off in the zebrafish, the team were able to study the multiple effects that this could have on hair cell direction.

This was made possible using new statistical characterizations developed at Cardiff University, which enabled the scientists to measure the types of hair cell patterns that would be created, for instance being highly aligned in rows, not aligned, or aligned in circular structures.

Results showed that not only could the regularity of the hair cell pattern be destroyed, producing a random hair cell direction, but certain alterations to the genes could lead to the hair cells having circular or spiral patterns.

First author Joaquin Navajas Acedo, Student at the Graduate School of the Stowers Institute for Medical Research, said: “The lateral line of zebrafish represents a unique tool to study this problem in particular, because of its accessibility and size. We are just beginning to understand the complex regulatory mechanisms behind this exciting process, and we hope more people start using this system to tackle the problem.”

Co-author of the study Dr Thomas Woolley, from Cardiff University’s School of Mathematics, said: “The big result is that we better understand what influences hair cell directionality and, equally, what may be going wrong in humans. These insights provide new directions through which we can tackle congenital hearing problems.”

The study involved scientists from Cardiff University, the Stowers Institute for Medical Research and the Fred Hutchinson Cancer Research Centre.

Reference: “PCP and Wnt pathway components act in parallel during zebrafish mechanosensory hair cell orientation” by Joaquin Navajas Acedo, Matthew G. Voas, Richard Alexander, Thomas Woolley, Jay R. Unruh, Hua Li, Cecilia Moens and Tatjana Piotrowski, 5 September 2019, Nature Communications.
DOI: 10.1038/s41467-019-12005-y

  声明:本文仅为传递更多网络信息,不代表马来西亚太子阁医药中心|官网|医院|生殖中心观点和意见,仅供参考了解,更不能作为投资使用依据。


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