Exploring a novel role of neural crest during otic vesicle morphogenesis

探索神经嵴在耳囊形态发生过程中的新作用

• 批准号: BB/M008517/1
• 负责人: Roberto Mayor
• 金额: $ 62.23万
• 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: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FM008517%2F1
• 关键词: Exploring; novel; role; neural; crest

The inner ear contains sensory epithelia that detect head movements, gravity and sound. Only recently some researchers have reached a moderate success in developing sensory epithelia from pluripotent stem cells by culturing inner ear stem cells in a 3D environment. It has been assumed that a 3D environment can mimic some of the properties present during normal embryo develop and that are required for stem cell establishment and proper differentiation. During normal development the inner ear is formed from a flat piece of tissue that is transformed by unknown mechanisms into a ball of cells with an internal cavity, called otic vesicle. Later this otic vesicle will give rise to all derivatives of the inner ear. The aim of this project is to generate a cellular, molecular and biomechanical explanation of how the otic vesicle is formed during normal development. In addition we will use this information to generate otic vesicles in vitro, which will allow understanding the intimate details of this complex morphogenetic process. This project will lay the foundations for future research concerning the generation of inner ear stem cells in vitro, essential for modelling inner ear disorders or developing cell-based therapies for profound hearing loss and balance disorders.

内耳含有感觉上皮，可以检测头部运动、重力和声音。直到最近，一些研究人员通过在 3D 环境中培养内耳干细胞，在利用多能干细胞发育感觉上皮方面取得了一定的成功。人们认为 3D 环境可以模拟正常胚胎发育过程中存在的一些特性，这些特性是干细胞建立和正确分化所需的。在正常发育过程中，内耳由一块平坦的组织形成，该组织通过未知的机制转化为具有内腔（称为耳囊）的细胞球。后来，这个耳泡将产生内耳的所有衍生物。该项目的目的是从细胞、分子和生物力学角度解释耳囊在正常发育过程中是如何形成的。此外，我们将利用这些信息在体外生成耳囊泡，这将有助于了解这一复杂形态发生过程的详细细节。该项目将为未来有关体外内耳干细胞生成的研究奠定基础，这对于模拟内耳疾病或开发针对严重听力损失和平衡障碍的细胞疗法至关重要。

项目成果

Cadherin Switch during EMT in Neural Crest Cells Leads to Contact Inhibition of Locomotion via Repolarization of Forces.

神经嵴细胞 EMT 期间的钙粘蛋白开关通过力的复极化导致运动的接触抑制。

• DOI: 10.1016/j.devcel.2015.06.012
• 发表时间: 2015-08-24
• 期刊: Developmental cell
• 影响因子: 11.8
• 作者: Scarpa E;Szabó A;Bibonne A;Theveneau E;Parsons M;Mayor R
• 通讯作者: Mayor R

Forcing contact inhibition of locomotion.

强迫接触运动。

• DOI: 10.1016/j.tcb.2015.05.001
• 发表时间: 2015-07
• 期刊: Trends in cell biology
• 影响因子: 19
• 作者: Roycroft A;Mayor R
• 通讯作者: Mayor R

Molecular basis of contact inhibition of locomotion.

• DOI: 10.1007/s00018-015-2090-0
• 发表时间: 2016-03
• 期刊: Cellular and molecular life sciences : CMLS
• 作者: Roycroft A;Mayor R
• 通讯作者: Mayor R

Chemotaxis during neural crest migration.

• DOI: 10.1016/j.semcdb.2016.01.031
• 发表时间: 2016-07
• 期刊: Seminars in cell & developmental biology
• 影响因子: 7.3
• 作者: Adam Shellard;R. Mayor

Collective cell migration in development.

• DOI: 10.1083/jcb.201508047
• 发表时间: 2016-01-18
• 期刊: The Journal of cell biology
• 作者: Scarpa E;Mayor R
• 通讯作者: Mayor R