How tissue mechanics control cell differentiationin vivo

组织力学如何控制体内细胞分化

• 批准号: BB/T013044/1
• 负责人: Roberto Mayor
• 金额: $ 64.76万
• 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: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FT013044%2F1
• 关键词: How; tissue; mechanics; control; cell

One of the central questions in biology is how a single cell, the fertilized oocyte, is able to generate hundreds of different cell types during embryonic development, like neurons, muscle, blood cells, etc.; answering this questions is not only essential for the biological sciences, but has deep implications in cell therapy. Mastering the transformation of one cell into a different one, called cell differentiation, would allow us to generate specific cell types to replace defective cells during regenerative therapies. For example, in neurogenerative diseases defective neurons need to be replaced by healthy ones that could be generated in vitro by cell differentiation. However, HOW A NON-NEURONAL CELL IS DIFFERENTIATED INTO A NEURON IS POORLY UNDERSTOOD. It is clear that cell differentiation is controlled by diverse cues, such as chemicals and mechanicals. While the role of chemical cues in controlling cell behaviour is comparatively well studied, how tissue mechanics influences cell differentiation remains unknown, especially in vivo, as most of biomechanical studies are performed in vitro. HERE WE WILL STUDY THE ROLE OF TISSUE MECHANICS ON THE DIFFERENTIATION OF NEURONS DURING EMBRYO DEVELOPMENT IN VIVO.We have developed special tools to manipulate the mechanical properties of live tissues in Xenopus embryos. We will use these tools to modify tissue stiffness in vivo followed by analysis of neuronal differentiation. In addition we will identify the molecules required to sense and transduce the mechanical cues into in vivo neuronal differentiation. The central aim of this proposal is to elucidate the fundamental principles underlying the interaction between cell mechanics and fate specification during embryo development. We expect that this transdisciplinary approach will provide answers to a central yet unresolved question in developmental biology: how the interplay between cell mechanics and fate specification drives embryo development.

生物学的核心问题之一是单个细胞，即受精卵，如何在胚胎发育过程中产生数百种不同类型的细胞，如神经元、肌肉、血细胞等；回答这个问题不仅对生物科学至关重要，而且对细胞治疗也有深远的影响。掌握一种细胞向另一种细胞的转化，称为细胞分化，将使我们能够在再生治疗中产生特定类型的细胞来取代有缺陷的细胞。例如，在神经发生性疾病中，有缺陷的神经元需要被健康的神经元取代，而健康的神经元可以在体外通过细胞分化产生。然而，非神经元细胞是如何分化成神经元细胞的，人们却知之甚少。很明显，细胞分化是由多种因素控制的，比如化学物质和机械因素。虽然化学信号在控制细胞行为中的作用已经得到了较好的研究，但组织力学如何影响细胞分化仍然未知，特别是在体内，因为大多数生物力学研究都是在体外进行的。我们将在体内研究组织力学在胚胎发育过程中神经元分化中的作用。我们已经开发了特殊的工具来操纵爪蟾胚胎中活组织的机械特性。我们将使用这些工具在体内修改组织刚度，然后分析神经元分化。此外，我们将确定感知和转导机械信号到体内神经元分化所需的分子。本提案的中心目的是阐明胚胎发育过程中细胞力学和命运规范之间相互作用的基本原理。我们期望这种跨学科的方法将为发育生物学中一个尚未解决的核心问题提供答案：细胞力学和命运规范之间的相互作用如何驱动胚胎发育。

项目成果

Author Correction: An optochemical tool for light-induced dissociation of adherens junctions to control mechanical coupling between cells

作者更正：一种光化学工具，用于光诱导粘附连接解离，以控制细胞之间的机械耦合

• DOI: 10.1038/s41467-020-15275-z
• 发表时间: 2020
• 期刊: Nature Communications
• 影响因子: 16.6
• 作者: Ollech D

RanBP1 plays an essential role in directed migration of neural crest cells during development

RanBP1 在神经嵴细胞发育过程中的定向迁移中发挥重要作用

• DOI: 10.1101/2022.05.05.490747
• 发表时间: 2022
• 作者: Barriga E

Mechanosensitive ion channels in cell migration.

• DOI: 10.1016/j.cdev.2021.203683
• 发表时间: 2021-06
• 期刊: Cells & development
• 影响因子: 3.9
• 作者: Canales Coutiño B;Mayor R
• 通讯作者: Mayor R

The mechanosensitive channel Piezo1 cooperates with semaphorins to control neural crest migration.

• DOI: 10.1242/dev.200001
• 发表时间: 2021-12-01
• 期刊: Development (Cambridge, England)
• 作者: Canales Coutiño B;Mayor R
• 通讯作者: Mayor R

Cell-matrix and cell-cell interaction mechanics in guiding migration.

• DOI: 10.1042/bst20230211
• 发表时间: 2023-08-31
• 期刊: Biochemical Society transactions
• 影响因子: 3.9