Tissue-Tissue Interactions at Boundaries of Colliding Monolayers

Classic ‘wound healing’ studies in epithelial monolayers use a wound or barrier removal to induce and study collective migration, focusing on the migration rather than the ultimate collision and tissue healing. Here, we address this by comprehensively studying epithelial tissue-tissue interactions in homotypic tissues from the initial outgrowth of multiple tissues through collision until a single, mature tissue is formed. We show the boundary between two non-mixing tissues is directly modulated by their size, shape, and density, and the boundary varies over time until the newly fused tissue stabilizes. In addition to characterizing interactions and boundary dynamics between colliding tissues, we predict the resulting fused tissue forms using a simple computational model assuming isotropic growth, which is used to systematically design the final resulting “mosaic” from many growing tissues. Finally, we show that unexpected boundary dynamics occur at the confluence of three or more tissues coming together that can lead to surprising planar extrusions where one tissue pushes out between converging neighboring tissues resulting in long, stretched regions of tissues.