title: E-cadherin plays an essential role in collective directional migration of large epithelial sheets.
abstract: In wound healing and development, large epithelial sheets migrate collectively, in defined directions, and maintain tight cell-cell adhesion. This type of movement ensures an essential function of epithelia, a barrier, which is lost when cells lose connection and move in isolation. Unless wounded, epithelial sheets in cultures normally do not have overall directional migration. Cell migration is mostly studied when cells are in isolation and in the absence of mature cell-cell adhesion; the mechanisms of the migration of epithelial sheets are less well understood. We used small electric fields (EFs) as a directional cue to instigate and guide migration of epithelial sheets. Significantly, cells in monolayer migrated far more efficiently and directionally than cells in isolation or smaller cell clusters. We demonstrated for the first time the group size-dependent directional migratory response in several types of epithelial cells. Gap junctions made a minimal contribution to the directional collective migration. Breaking down calcium-dependent cell-cell adhesion significantly reduced directional sheet migration. Furthermore, E-cadherin blocking antibodies abolished migration of cell sheets. Traction force analysis revealed an important role of forces that cells in the leading rows exert on the substratum. With EF, the traction forces of the leading edge cells coordinated in directional re-orientation. Our study thus identifies a novel mechanism--E-cadherin dependence and coordinated traction forces of leading cells in collective directional migration of large epithelial sheets.
authors.affiliation: Department of Dermatology, School of Medicine, Institute for Regenerative Cures, University of California at Davis, Suite 1630, 2921 Stockton Blvd., Room 1617, Sacramento, CA 95817, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Robert
authors.initials: R
authors.lastname: Hartley
authors.forename: Bjoern
authors.initials: B
authors.lastname: Reiss
authors.forename: Yaohui
authors.initials: Y
authors.lastname: Sun
authors.forename: Jin
authors.initials: J
authors.lastname: Pu
authors.forename: Dan
authors.initials: D
authors.lastname: Wu
authors.forename: Francis
authors.initials: F
authors.lastname: Lin
authors.forename: Trung
authors.initials: T
authors.lastname: Hoang
authors.forename: Soichiro
authors.initials: S
authors.lastname: Yamada
authors.forename: Jianxin
authors.initials: J
authors.lastname: Jiang
authors.forename: Min
authors.initials: M
authors.lastname: Zhao
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002417:Cattle; D002448:Cell Adhesion; D002450:Cell Communication; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D004285:Dogs; D004553:Electric Conductivity; D019573:Epithelium, Corneal / Q000166:cytology / Q000378:metabolism*; D017629:Gap Junctions / Q000502:physiology*; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D014132:Trachea / Q000166:cytology / Q000378:metabolism*
chemical_list: D015820:Cadherins