Mechanical force-driven cell competition ensures robust morphogen gradient formation

Abstract

Morphogen gradients provide positional data and maintain tissue patterns by instructing cells to adopt distinct fates. In contrast, morphogen gradient-forming tissues undergo dynamic morphogenetic movements that generate mechanical forces and can disturb morphogen signal transduction. However, the interactions between morphogen gradients and these forces remain largely unknown. In this study, we described how mechanical force-mediated cell competition corrects noisy morphogen gradients to ensure robust tissue patterns. The Wnt/β-catenin morphogen gradient—that patterns the embryonic anterior-posterior axis—generates cadherin-actomyosin interaction-mediated intercellular tension gradients—termed mechano-gradients. Naturally generated unfit cells that produce noisy Wnt/β-catenin gradients induce local deformation of the mechano-gradients. Neighboring fit cells sense this deformation, resulting in the activation of Piezo family mechanosensitive calcium channels and secretion of annexinA1, which specifically kills unfit cells to recover morphogen gradients. Therefore, mechanical force-mediated cell competition between the morphogen-receiver cells supports robust gradient formation. Additionally, we discuss the potential roles of mechanical force-driven cell competition in other contexts, including organogenesis and cancer.