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Tissue boundary formation in the embryonic inner ear: cellular mechanisms and molecular effectors

胚胎内耳的组织边界形成：细胞机制和分子效应器

基本信息

批准号：
BB/L003163/1
负责人：
Nicolas Daudet
金额：
$ 57.18万
依托单位：
University College London
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2014
资助国家：
英国
起止时间：
2014 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FL003163%2F1
关键词：
Tissue boundary formation embryonic inner

项目摘要

The very elaborate structure and function of the vertebrate inner ear, containing the sensory organs for hearing and balance, have been shaped by millions of years of evolution. Fish and reptiles have a simple inner ear, which contains a small number of sensory patches and relatively poor hearing capability. In birds and mammals, the increase in number of sensory patches and the accompanying changes in inner ear architecture have led to the acquisition of ever more specialized vestibular and auditory functions. The formation of the inner ear during embryonic life seems to recapitulate this evolutionary history: most of the sensory patches originate from a common 'prosensory' region by progressive segregation. However the signals that control this segregation and establish the spatial boundaries of sensory domains remain mysterious. The aim of this project is to tackle this question in the chicken and mouse embryonic inner ear, using a combination of functional and 'gene discovery' approaches. We will analyse the character and dynamic behaviour of cells during the formation of the boundaries between sensory and non-sensory domains of the inner ear. We will also use new DNA sequencing technologies to unravel the key genetic programs that underlie sensory patch segregation. Besides providing new insights into the mechanisms of formation and evolution of one of our major sense organs, this work could lead to the identification of new genes critical for ear development and function. This is crucial for improving the diagnosis of hereditary forms of deafness and accelerating the development of the 'next-generation' gene and stem cell therapies for hearing loss.

脊椎动物的内耳包含了听觉和平衡的感觉器官，其复杂的结构和功能是经过数百万年的进化形成的。鱼类和爬行动物有一个简单的内耳，内耳包含少量的感觉补丁，听力能力相对较差。在鸟类和哺乳动物中，感觉斑块数量的增加和内耳结构的变化导致了更专门的前庭和听觉功能的获得。胚胎时期内耳的形成似乎概括了这一进化历史：大多数感觉斑块起源于一个共同的“前感觉”区域，并逐渐分离。然而，控制这种分离并建立感觉域空间边界的信号仍然是神秘的。这个项目的目的是在鸡和老鼠的胚胎内耳中解决这个问题，使用功能和“基因发现”方法的结合。我们将分析在内耳的感觉和非感觉领域之间的边界形成过程中细胞的特征和动态行为。我们还将使用新的DNA测序技术来揭示构成感官斑块分离的关键遗传程序。除了为我们的主要感觉器官之一的形成和进化机制提供新的见解外，这项工作还可能导致鉴定对耳朵发育和功能至关重要的新基因。这对于改善遗传性耳聋的诊断和加速开发针对听力损失的“下一代”基因和干细胞疗法至关重要。

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Editorial.

社论。

DOI：
10.1016/j.semcdb.2017.04.005
发表时间：
2017
期刊：
Seminars in cell & developmental biology
影响因子：
7.3
作者：
Stone JS
通讯作者：
Stone JS

A tissue boundary orchestrates the segregation of inner ear sensory organs

组织边界协调内耳感觉器官的分离

DOI：
10.1101/2022.03.03.482809
发表时间：
2022
期刊：
影响因子：
0
作者：
Chen Z
通讯作者：
Chen Z

Shaping of inner ear sensory organs through antagonistic interactions between Notch signalling and Lmx1a.

DOI：
10.7554/elife.33323
发表时间：
2017-12-04
期刊：
eLife
影响因子：
7.7
作者：
Mann ZF;Gálvez H;Pedreno D;Chen Z;Chrysostomou E;Żak M;Kang M;Canden E;Daudet N
通讯作者：
Daudet N

Numb is not a critical regulator of Notch-mediated cell fate decisions in the developing chick inner ear.