During development, thousands of cells coordinate to migrate and organize into diverse 3D shapes of tissues and organs of our body. It is now well established that mechanics is essential to tissue morphogenesis, where spatiotemporally specific mechanical forces guide large-scale tissue assembly (e.g., elongation and folding), cell shape changes, and transitions in cell plasticity. However, it is still not clear how cell-scale components (e.g., intracellular cytoskeletal machinery, intercellular adhesions, and cell shape changes) mechanically integrate to establish the final architecture of tissues, organs, and body. My career has been dedicated to probing the dynamic physical and cellular behaviors of 3D tissue formation. I have identified, characterized, and manipulated the force-generating cellular behaviors (e.g., shape changes, collective movements, differentiation, and assembly of matrix) and mechanical modules (e.g., cell-cell or –matrix adhesion, contractility, and protrusion) that contribute to the tissue morphogenesis such as the pulsatile actomyosin network during tissue narrowing and extension , the apical constriction during initial folding of airway epithelium, localized smooth muscle differentiation that splits the end bud during branching morphogenesis of the lung, and how tissue mechanics drives cell phenotypic transition and lineage specification in embryonic cell aggregates by utilizing multiple model organisms, including mouse, chicken, and frog. In this talk I will introduce these previous efforts and share the recent progress in understanding the role of mechanics of microenvironment during regeneration of mucociliary epidermis and metastatic colonization.