Rho-dependent formation of epithelial "leader" cells during wound healing

T. Omelchenko, J. M. Vasiliev, I. M. Gelfand, H. H. Feder, E. M. Bonder

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The motile behavior of epithelial cells located at the edge of a large wound in a monolayer of cultured cells was analyzed. The initial cellular response is alignment of the edge with an accompanying formation of tangential marginal actin bundles within individual cells positioned along the wound edge. Later, coherent outgrowths of cell masses occur by the formation of special "leader" cells at the tops of outgrowths and "follower" cells along the sides. Leader cells exhibit profound cytoskeletal reorganization, including disassembly of marginal bundles, the realignment of actin filament bundles, and penetration of microtubules into highly active lamellae. Additionally, cell-cell contacts acquire radial geometry indicative of increased contractile tension. Interestingly, leader cells acquire a cytoskeletal organization and motility typical of fibroblasts. IAR-2 cultures stably transfected with a dominant-negative mutant of RhoA or treated with Rho-kinase inhibitor Y-27632 transformed most edge cells into leader-like cells. Alternatively, transfection of cells with constitutively active RhoA suppressed formation of leaders. Thus, expansion of the epithelial sheet involves functional differentiation into two distinct types of edge cells. The transition between these two patterns is controlled by Rho activity, which in turn controls the dynamic distribution and activity of actin filament bundles, myosin II, and microtubules.

Original languageEnglish (US)
Pages (from-to)10788-10793
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number19
StatePublished - Sep 16 2003

All Science Journal Classification (ASJC) codes

  • General


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