Collective Regulation of Cell Decisions

Developing systems show an unmatched complexity due to an entangled regulation across different levels of organization. Errors in this regulation often lead to tissue and organ malformations and disease.

Accordingly, cell decisions like division, fate or motility are not only guided by local signals generated at the cell micro-environment, but also integrate cues propagated by collective properties at the tissue-level, such as tissue rigidity.

How the cell’s macro-environment impacts cell decisions is still elusive, largely because we lack methods and concepts to identify and eventually control collective tissue properties.

I will tackle this question by harnessing the physics of collective behaviours as design principles for synthetic in vivo developmental biology.

We build on our discovery that embryonic tissue rigidity emerges via phase transitions, only when a simple cell parameter, cell connectivity, reaches a specific but generic value, the critical point.

By identifying the responsible cell parameters and their critical points, we will build tools to tune those parameters, engineer for the first time, a set of tissue physical properties in vivo and explore their role in cell decisions.

We will use the developing zebrafish as a model and: Quantitatively map cell parameters and the critical points at which tissue properties emerge; Control tissue properties by opto-genetically tuning the responsible cell parameters in relation to the critical points; Dissect mechanisms of collective regulation of cell polarity and fate decisions at single-cell resolution; Derive generic principles of multiple cell decision-making by comparing species operating near or far from critical points.

Uncovering how collective properties impact cell decisions will reveal mechanisms of tissue development transcending biological scales, generate new hypotheses of how developing systems optimise biological functions, and inform strategies for tissue engineering and disease treatment.