The study investigates the molecular and mechanical processes that drive the formation of intestinal villi, which are finger-like protrusions that enhance nutrient absorption. The research identifies an active mechanical mechanism where subepithelial mesenchymal cells, specifically those expressing PDGFRA, generate forces that fold the intestinal epithelium, initiating villus formation. These forces are mediated by myosin II-dependent contractions and are sufficient to produce patterned curvature in the tissue interface. The process involves altered cell and extracellular matrix interactions, facilitated by matrix metalloproteinase-mediated tissue fluidization. Computational models and in vitro/in vivo experiments reveal that these cellular features manifest as differences in interfacial tensions, promoting mesenchymal aggregation and interface bending. The study also highlights the role of integrin-mediated cell-ECM interactions in aggregate compaction and proper interfacial folding. The findings provide a comprehensive understanding of how the subepithelial mesenchyme, through active dewetting-like processes, patterns and folds the intestinal epithelium to initiate villus formation.The study investigates the molecular and mechanical processes that drive the formation of intestinal villi, which are finger-like protrusions that enhance nutrient absorption. The research identifies an active mechanical mechanism where subepithelial mesenchymal cells, specifically those expressing PDGFRA, generate forces that fold the intestinal epithelium, initiating villus formation. These forces are mediated by myosin II-dependent contractions and are sufficient to produce patterned curvature in the tissue interface. The process involves altered cell and extracellular matrix interactions, facilitated by matrix metalloproteinase-mediated tissue fluidization. Computational models and in vitro/in vivo experiments reveal that these cellular features manifest as differences in interfacial tensions, promoting mesenchymal aggregation and interface bending. The study also highlights the role of integrin-mediated cell-ECM interactions in aggregate compaction and proper interfacial folding. The findings provide a comprehensive understanding of how the subepithelial mesenchyme, through active dewetting-like processes, patterns and folds the intestinal epithelium to initiate villus formation.