Abstract

Abstract: 

Morphogenesis relies on the precise coordination of single-cell behaviors to build complex tissues. Intestinal development exemplifies this process, as crypt formation emerges from tightly regulated biochemical and mechanical cues. Using organoid models combined with in vivo studies, we dissect how crypt morphogenesis is initiated by actomyosin-driven apical constriction and accelerated by osmotic forces. We identify a critical mechanochemical feedback loop mediated by calcium-dependent cytosolic phospholipase A2 (cPLA2), which senses mechano-osmotic changes and triggers robust crypt formation via arachidonic acid production and myosin relocalization. Together, our work reveals how cells integrate mechanical and osmotic signals to orchestrate irreversible tissue-scale transformations during development.