Towards a multiscale understanding of heart morphogenesis

Heart is the first functional organ in a developing embryo. One critical step during vertebrate heart development is trabeculation, which is crucial for heart function. During trabeculation, the myocardial wall transforms from a single-layered epithelium into a complex topological structure consisting of two distinct cell fates – outer compact layer and inner trabecular layer cardiomyocytes (CMs). 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 spatial 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 taking a systems-level multiscale approach, my lab aims to resolve how a primitive myocardial wall transforms from a simple epithelium into a 3D intricate functional tissue. In this seminar, I will be discussing some of our previous and current findings explaining how morphological complexity is built up during cardiac trabeculation.

SPEAKER BIOGRAPHY

Rashmi has diverse research interests and her career has spanned across three continents. She did her Masters from India where she was supported by competitive scholarships to work on the cell biology of malaria parasites (JNU, New Delhi) and cancer metastasis (CRI-TMC, Mumbai). For her PhD, Rashmi secured international PhD fellowships and moved to Australia, to work with Alpha Yap at IMB, UQ. During her PhD, she discovered novel signalling pathways required to maintain epithelial tissue integrity during health and disease. For her post-doctoral training, Rashmi moved to Germany to work with Didier Stainier at Max Planck Institute for Heart and Lung Research, Germany. She was awarded fellowships from EMBO and Humboldt foundation and a DFG research grant. During her post-doc, Rashmi used her interdisciplinary background to provide novel insights into cardiac trabeculation, a less understood process critical for heart function. In February 2021, Rashmi started her own lab at the Francis Crick Institute, London. Her lab integrates developmental genetics and quantitative cell/tissue mechanics to address how organs are shaped inside a developing embryo.