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

Informations projet

MechanoSelfFate

N° de convention de subvention: 866186

DOI

10.3030/866186

Date de signature de la CE 6 Mars 2020

Date de début 1 Septembre 2020

Date de fin 31 Août 2026

Financé au titre de

• EXCELLENT SCIENCE - European Research Council (ERC)

Coût total

€ 1 995 334,00

Contribution de l’UE

€ 1 995 334,00

Coordonné par

INSTITUT PASTEUR
France

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

Période du rapport: 2023-09-01 au 2025-02-28

Résumé du contexte et des objectifs généraux du projet

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.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

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.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

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