How tissue mechanics control cell differentiationin vivo

点击翻译按钮获取中文摘要

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.