Mechanochemical coupling of cell shape and organ function optimizes heart size and contractile efficiency in zebrafish

How simple tissue primordia sculpt complex functional organs, robustly and reproducibly, remains elusive. During zebrafish development, the embryonic myocardial wall matures into an intricate 3D architecture, composed of an outer compact layer enveloping an inner layer of multicellular trabecular ridges. How these tissue layers acquire their characteristic form suited for their function remains an open question. Here, we find that multiscale mechanochemical coupling and an emergent tissue-scale morphological transition steer functional maturation of the developing zebrafish heart. Single-celled trabecular seeds recruit outer compact layer cells to mature into clonally heterogeneous multicellular ridges, thereby amplifying cardiac contractile forces. In response, the remaining compact layer cells are stretched, which impedes their further recruitment, thereby constraining trabecular ridge density. Concomitantly, Notch-dependent actomyosin dampening triggers a sharp transition in myocardial tissue area, activating rapid organ growth that expands blood-filling capacity. Thus, multiscale self-organizing interactions optimize heart size and contractile efficiency to support embryonic life.