Mechanical fracturing of the extracellular matrix patterns the vertebrate heart

Abstract

Pattern formation is fundamental to embryonic morphogenesis. In the zebrafish heart, spatially confined single-cell delamination in the ventricle outer curvature initiates trabeculation, a conserved morphogenetic process critical for heart function and embryonic life. Yet, what confines delamination in the ventricle outer curvature remains ill-understood. Contrary to the prevailing notion of patterning through biochemical signals, we now show that mechanical fracturing of the cardiac extracellular matrix (cECM) patterns delamination in the outer curvature. cECM fractures emerge preferentially in the outer curvature, cells delaminate into these fractures and experimental blocking of fractures blocks delamination. These fractures display characteristic signature of mechanical defects and myocardial tissue contractility is sufficient to fracture the cECM, independent of molecular signals, enzymatic activity, or delamination events. Notably, the anisotropic geometry of myocardial tissue generates higher mechanical strain in the outer curvature, thereby locally patterning cECM fractures and delamination. Consequently, cECM fractures evolve in response to dynamic changes in tissue geometry, and experimental manipulation of tissue geometry is sufficient to alter the fracture pattern. Together, our findings underscore mechanical fractures as a morphogenetic strategy, and more generally, corroborate the long-standing but understudied paradigm that tissue form-function can feed back to steer its own patterning.