Co-ordination of tissue morphogenesis and cell fate specification during development

In this, Priya et al set out to determine how differential tension heterogeneity and cellular mechanics generate higher order patterning and diversifies cell fate in the developing zebrafish heart. They use elegant genetic and live imaging experiments to ask how a single layer epithelium can transform into a complex 3-D structure during the process of trabeculation, which takes place early in heart development and is crucial for heart function. Thus, in the single cardiomyocyte compact layer (CL), a subset of cells acquire higher actinomyosin tension, constrict their apical domain and delaminate to seed the trabecular layer (TL). This differential tension (heterogeneity) and delamination arises in response to crowding and compressive strain caused by growth of the CL. Proliferation is controlled by the Erbb2 pathway, as inhibitors of this pathway can block trabeculation. The Nrg/Erbb pathway is crucial for trabeculation in vertebrates and nrg2a morphants do not develop trabeculae. Rescue experiments show that by inducing mosaic contractility in these morphants, cells delaminate normally and form trabecular ridges in the same way as control embryos. Moreover, they find that manipulating the delamination process by controlling the contractility of delaminating cardiomyocytes also rescues the nrg2a defect. The myocardial compact versus trabecular fate are controlled by the cell fate regulator Notch, which is activated in cells in the CL adjacent to delaminating cells. Notch restricts cell delamination via lateral inhibition, downregulating contractility. Ectopic Notch activity can be induced by activating delamination, and Notch activation can be rescued in the nrg2a morphant by activating contractility, suggesting that contractility-induced cell delamination is sufficient to trigger differential Notch activation. Thus, by showing how cardiomyocyte form and fate feedback on each other to pattern the developing ventricle, the work of Priya et al. provides a striking example of how tissue morphogenesis and cell fate specification are coordinated during development.