University of Cambridge > > Morphogenesis Seminar Series > Building organs – emergence of form and fate through local force imbalance

Building organs – emergence of form and fate through local force imbalance

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  • UserRashmi Priya, The Francis Crick Institute, London World_link
  • ClockMonday 14 June 2021, 14:30-15:30
  • HouseOnline.

If you have a question about this talk, please contact Elena Scarpa.

How diverse cell fates and complex forms emerge and interact across scales during organogenesis remains unknown. A critical step during vertebrate heart development is trabeculation, during which the primitive heart transforms from a simple epithelium to an intricate topological structure consisting of two distinct cell types – outer compact and inner trabecular layer cardiomyocytes (CMs). Trabeculation defects cause cardiomyopathies and embryonic lethality, yet how tissue symmetry is broken to specify trabecular CMs is unknown. We now report that local tension heterogeneity drives organ-scale patterning and cell fate decisions during zebrafish cardiac trabeculation. Tissue-scale crowding induces local differences in CM contractility, which subsequently triggers stochastic delamination of CMs from the outer compact layer to seed the inner trabecular layer. CMs with higher contractility delaminate, even in the absence of critical biochemical regulators (Nrg/Erbb2) to seed the trabecular layer. Notably, mechanics direct CM fate specification, as mechanical segregation of CMs into compact versus trabecular layer is sufficient to induce differential Notch activity and apicobasal polarity. Notch in turn suppresses CM actomyosin machinery to limit excessive delamination, thereby preserving the myocardial wall architecture. Thus, multiscale synergistic interactions between mechanical forces and cell fate ensures robust self-organized organ patterning.

This talk is part of the Morphogenesis Seminar Series series.

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