University of Cambridge > > Theory of Living Matter Group > Tension heterogeneity instructs morphogenesis and fate specification during heart development

Tension heterogeneity instructs morphogenesis and fate specification during heart development

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If you have a question about this talk, please contact Dr. Adrien Hallou.

How ordered complexity (form and fate) emerges in vivo during organogenesis is ill understood. A critical step during vertebrate heart development is trabeculation, during which the myocardial wall transforms from a monolayer to a complex topological structure consisting of two distinct cell types: outer compact layer (CL) and inner trabecular layer (TL) cardiomyocytes (CMs). Cardiac trabeculation is crucial for heart function. Yet, the mechanisms underlying the emergence and specification of trabecular CMs remain unknown. Using the zebrafish heart in combination with in vivo quantitative imaging, measurements of tension and genetic mosaic tools, we now report that tension heterogeneity drives morphogenesis as well as cell fate decisions during heart morphogenesis. Proliferation induced crowding generates tension heterogeneity among CL C Ms thus driving their delamination from the outer to the inner layer. Inducing contractility augments CM delamination and strikingly rescues delamination even in absence of critical trabeculation signals. Notably, mechanical segregation of CMs into compact versus trabecular layer is necessary and sufficient to trigger differential CM fate by inducing differential Notch activity. Broadly, these findings argue for a system-level approach integrating mechanics with regulatory circuits for a cogent understanding of organ development.

This talk is part of the Theory of Living Matter Group series.

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