University of Cambridge Morphogenesis Seminar Series is a series of weekly online seminars on the topic of Morphogenesis. Talks are on Mondays at 2:30pm during term time and are given by both international and local speakers. The seminars are open to all.
Speakers represent the diverse topics that make up morphogenesis, including biomechanics, cell and tissue level interactions, theoretical analyses and modelling, and different systems such as animals, plants, and single cell approaches.
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14/6 Rashmi Priya
Title: Building organs – emergence of form and fate through local force imbalance
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.