Role of Tissue Mechanics in Embryonic Self-Organization and Cell Fate Plasticity

Project Information

MechanoSelfFate

Grant agreement ID: 866186

DOI

10.3030/866186

EC signature date 6 March 2020

Start date 1 September 2020

End date 31 August 2026

Funded under

• EXCELLENT SCIENCE - European Research Council (ERC)

Total cost

€ 1 995 334,00

EU contribution

€ 1 995 334,00

Coordinated by

INSTITUT PASTEUR
France

Periodic Reporting for period 3 - MechanoSelfFate (Role of Tissue Mechanics in Embryonic Self-Organization and Cell Fate Plasticity)

Reporting period: 2023-09-01 to 2025-02-28

Summary of the context and overall objectives of the project

The nature of the interactions between molecular and mechanical information that coordinate morphogenesis and cell differentiation during development remains largely unknown. The avian embryo, which exhibits highly regulatory development and is highly amenable to dynamic imaging approaches as well as mechanical perturbations, is an ideal model for studying such interactions. Based on recent results characterizing the mechanical control shaping the early embryo, we propose a programme integrating experiments and theory with the aim of i) testing whether a self-organizing mechanical system participates in the regulatory potential of the avian embryo; ii) elucidating the role of mechanical forces in cell fate acquisition. These studies aim to reveal different levels of interaction between cellular, molecular and mechanical signals ensuring the specification and robust, yet plastic, allocation of cell fate.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

In this project, we have established novel ways to interfere mechanically with live quail embryos. This is possible because of bird embryo's accessibility and high amenability to live imaging approaches, enabling us to perform perturbations and to monitor the effect of these perturbations by simultaneous live imaging. Using these mechanical perturbations, we show that the redirection of endogenous forces entails the redirection of gene expression. We conclude that the mechanical forces that shape the early embryo self-organize and regulate gene expression to promote the formation of a single, and well-proportioned embryo. Our findings, so far, demonstrate that the extraordinary regulative potential of the early embryo, (i.e. its ability to adapt to perturbations and variation), originates from a biomechanical self-organized module.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

Our results, change the way one think about the role of mechanical forces in biology, to show that they can self-organize in relative independence of molecular regulation and also that they can organize embryonic patterning by impinging on critical gene expression.
We are now investigating further the links between mechanical force and gene expression. By the end of this project, we expect to elucidate the cellular events (deformation, division, rearrangements , extrusions) underlying force generation regulation and the mechanosensitive pathways underlying the activation of gene expression.

forces and flows shaping the early embryo