title: Integrin adhesion drives the emergent polarization of active cytoskeletal stresses to pattern cell delamination.
abstract: Tissue patterning relies on cellular reorganization through the interplay between signaling pathways and mechanical stresses. Their integration and spatiotemporal coordination remain poorly understood. Here we investigate the mechanisms driving the dynamics of cell delamination, diversely deployed to extrude dead cells or specify distinct cell fates. We show that a local mechanical stimulus (subcellular laser perturbation) releases cellular prestress and triggers cell delamination in the amnioserosa during Drosophila dorsal closure, which, like spontaneous delamination, results in the rearrangement of nearest neighbors around the delaminating cell into a rosette. We demonstrate that a sequence of "emergent cytoskeletal polarities" in the nearest neighbors (directed myosin flows, lamellipodial growth, polarized actomyosin collars, microtubule asters), triggered by the mechanical stimulus and dependent on integrin adhesion, generate active stresses that drive delamination. We interpret these patterns in the language of active gels as asters formed by active force dipoles involving surface and body stresses generated by each cell and liken delamination to mechanical yielding that ensues when these stresses exceed a threshold. We suggest that differential contributions of adhesion, cytoskeletal, and external stresses must underlie differences in spatial pattern.
authors.affiliation: Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai 400005, India.
authors.forename: C
authors.initials: C
authors.lastname: Meghana
authors.forename: Nisha
authors.initials: N
authors.lastname: Ramdas
authors.forename: Feroz Meeran
authors.initials: FM
authors.lastname: Hameed
authors.forename: Madan
authors.initials: M
authors.lastname: Rao
authors.forename: G V
authors.initials: GV
authors.lastname: Shivashankar
authors.forename: Maithreyi
authors.initials: M
authors.lastname: Narasimha
mesh_terms: D000205:Actomyosin / Q000737:chemistry; D000818:Animals; D002448:Cell Adhesion; D019070:Cell Lineage; D003593:Cytoplasm / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism*; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000378:metabolism; D016023:Integrins / Q000378:metabolism*; D018613:Microscopy, Confocal / Q000379:methods; D008954:Models, Biological; D013997:Time Factors; D014945:Wound Healing
chemical_list: D029721:Drosophila Proteins; D016023:Integrins; D049452:Green Fluorescent Proteins; D000205:Actomyosin