Tissue folds are essential for organ function, particularly in the intestine, where the folding of a flat epithelium into a periodic pattern of folds forms villi, which enhance nutrient absorption. This study identifies an active mechanical mechanism that patterns and folds the intestinal epithelium to initiate villus formation. Subepithelial mesenchymal cells generate myosin II-dependent forces that produce patterned curvature in neighboring tissue interfaces. This symmetry-breaking process requires altered cell and extracellular matrix interactions enabled by matrix metalloproteinase-mediated tissue fluidization. Computational models, along with in vitro and in vivo experiments, reveal that these cellular features manifest at the tissue level as differences in interfacial tensions that promote mesenchymal aggregation and interface bending through a process analogous to active dewetting of a thin liquid film. The study shows that PDGFRA+ subepithelial mesenchymal cells generate forces sufficient to produce patterned curvature in neighboring tissue interfaces. These cells aggregate and form villus clusters, which are essential for initiating villus formation. The aggregation of PDGFRA+ cells is sufficient to drive interfacial folding and initiate villi. The mesenchyme behaves as an active fluid whose morphology is dictated by surface tensions acting at its interface with surrounding tissue layers. The study also identifies that mesenchymal aggregation is sufficient to direct interfacial folding to initiate villi. PDGFRA+ cells aggregate and form villus clusters, which are essential for initiating villus formation. The aggregation of PDGFRA+ cells is sufficient to drive interfacial folding and initiate villi. The mesenchyme behaves as an active fluid whose morphology is dictated by surface tensions acting at its interface with surrounding tissue layers. The study further shows that mesenchymal non-muscle myosin activity drives cell motility, aggregation, and villus formation. Non-muscle myosin activity is required for mesenchymal aggregation and villus initiation. The study demonstrates that PDGFRA+ cells aggregate and form villus clusters, which are essential for initiating villus formation. The aggregation of PDGFRA+ cells is sufficient to drive interfacial folding and initiate villi. The mesenchyme behaves as an active fluid whose morphology is dictated by surface tensions acting at its interface with surrounding tissue layers. The study also identifies that integrin-mediated cell interactions are required for proper mesenchymal aggregation and compaction. Integrin-mediated cell interactions are necessary for aggregate compaction, regular patterning, and proper interfacial folding. The study shows that PDGFRA+ cells aggregate and form villus clusters, which are essential for initiating villus formation. The aggregation of PDGFRA+ cells is sufficient to drive interfacial folding and initiate villi. The mesenchyme behaves as an active fluid whose morphology is dictated by surface tensions acting at its interface with surrounding tissue layers. The study further shows that the loss of cell and ECMTissue folds are essential for organ function, particularly in the intestine, where the folding of a flat epithelium into a periodic pattern of folds forms villi, which enhance nutrient absorption. This study identifies an active mechanical mechanism that patterns and folds the intestinal epithelium to initiate villus formation. Subepithelial mesenchymal cells generate myosin II-dependent forces that produce patterned curvature in neighboring tissue interfaces. This symmetry-breaking process requires altered cell and extracellular matrix interactions enabled by matrix metalloproteinase-mediated tissue fluidization. Computational models, along with in vitro and in vivo experiments, reveal that these cellular features manifest at the tissue level as differences in interfacial tensions that promote mesenchymal aggregation and interface bending through a process analogous to active dewetting of a thin liquid film. The study shows that PDGFRA+ subepithelial mesenchymal cells generate forces sufficient to produce patterned curvature in neighboring tissue interfaces. These cells aggregate and form villus clusters, which are essential for initiating villus formation. The aggregation of PDGFRA+ cells is sufficient to drive interfacial folding and initiate villi. The mesenchyme behaves as an active fluid whose morphology is dictated by surface tensions acting at its interface with surrounding tissue layers. The study also identifies that mesenchymal aggregation is sufficient to direct interfacial folding to initiate villi. PDGFRA+ cells aggregate and form villus clusters, which are essential for initiating villus formation. The aggregation of PDGFRA+ cells is sufficient to drive interfacial folding and initiate villi. The mesenchyme behaves as an active fluid whose morphology is dictated by surface tensions acting at its interface with surrounding tissue layers. The study further shows that mesenchymal non-muscle myosin activity drives cell motility, aggregation, and villus formation. Non-muscle myosin activity is required for mesenchymal aggregation and villus initiation. The study demonstrates that PDGFRA+ cells aggregate and form villus clusters, which are essential for initiating villus formation. The aggregation of PDGFRA+ cells is sufficient to drive interfacial folding and initiate villi. The mesenchyme behaves as an active fluid whose morphology is dictated by surface tensions acting at its interface with surrounding tissue layers. The study also identifies that integrin-mediated cell interactions are required for proper mesenchymal aggregation and compaction. Integrin-mediated cell interactions are necessary for aggregate compaction, regular patterning, and proper interfacial folding. The study shows that PDGFRA+ cells aggregate and form villus clusters, which are essential for initiating villus formation. The aggregation of PDGFRA+ cells is sufficient to drive interfacial folding and initiate villi. The mesenchyme behaves as an active fluid whose morphology is dictated by surface tensions acting at its interface with surrounding tissue layers. The study further shows that the loss of cell and ECM