Tissue mechanics sets developmental scaling of collective cell migration

Abstract

Despite substantial variation in adult size, animals within a species maintain consistent tissue patterns and shapes, a core property known as developmental scaling or size invariance. Developmental scaling has predominantly been attributed to the scaling of morphogen gradients and gene patterns to maintain positional information and cell fate specification1,2. However, development also necessitates collective cell flows that reshape tissues and reposition cells3,4. How these flows adapt to body size remains unclear. By combining quantitative live imaging, experimental perturbations, and physical modeling in the Drosophila thorax epithelium, we address this question in the context of a fundamental process: collective cell migration. We find that migration velocity scales linearly with tissue size, accounting for size-invariant cell positioning. While gene patterning scales with tissue size and modulates force generation, it is not sufficient to ensure proper velocity scaling. Instead, tissue mechanical properties govern the dependence of migration velocity on tissue size, enabling developmental scaling within the physiological range of animal sizes. These findings uncover principles and limits of size invariance by revealing how tissue mechanics sets the scaling behavior of collective cell flows with organismal size.