Sculpting a Heart – multiscale interactions between Form, Forces, Fate and Function

Speaker Dr Rashmi Priya, Crick/BHF Group Leader, The Francis Crick Institute

Title Sculpting a Heart – multiscale interactions between Form, Forces, Fate and Function

Host Jody Rosenblatt

 

Abstract A long-standing question in developmental biology is how a simple tissue primordium gets moulded into 3D functional organs during embryogenesis. A critical step during vertebrate heart development is trabeculation, during which the myocardial epithelium transforms from a monolayer to a topological 3D meshwork. Trabeculae are multicellular ridges critical for heart function and anomalous trabecular morphology leads to cardiac defects and embryonic lethality. We have recently shown that local differences in the mechanical properties of CMs trigger this morphological symmetry breaking. CMs with higher mechanical tension delaminate stochastically to seed the trabecular layer, and this mechanical segregation is also sufficient to induce their differential fate. Eventually, these single trabecular cells grow into multicellular ridges, which remodel to form macroscopic topological trabecular meshwork thereby thickening the myocardial wall. How a developing heart acquires these crucial anatomical structures remains unknown. By exploiting excellent tractability of zebrafish heart with cross-disciplinary tools, my lab aims to decode the design rules underlying this morphogenetic transition. In this seminar, I will be discussing some of our previous and current findings explaining how morphological complexity is built up during cardiac trabeculation.