title: Mechanical feedback through E-cadherin promotes direction sensing during collective cell migration.
abstract: E-cadherin is a major homophilic cell-cell adhesion molecule that inhibits motility of individual cells on matrix. However, its contribution to migration of cells through cell-rich tissues is less clear. We developed an in vivo sensor of mechanical tension across E-cadherin molecules, which we combined with cell-type-specific RNAi, photoactivatable Rac, and morphodynamic profiling, to interrogate how E-cadherin contributes to collective migration of cells between other cells. Using the Drosophila ovary as a model, we found that adhesion between border cells and their substrate, the nurse cells, functions in a positive feedback loop with Rac and actin assembly to stabilize forward-directed protrusion and directionally persistent movement. Adhesion between individual border cells communicates direction from the lead cell to the followers. Adhesion between motile cells and polar cells holds the cluster together and polarizes each individual cell. Thus, E-cadherin is an integral component of the guidance mechanisms that orchestrate collective chemotaxis in vivo.
authors.affiliation: Department of Biological Chemistry, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA; Molecular, Cellular and Developmental Biology Department, University of California, Santa Barbara, Santa Barbara, CA 93106-9625, USA.
authors.forename: Danfeng
authors.initials: D
authors.lastname: Cai
authors.affiliation: Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037-1000, USA.
authors.forename: Shann-Ching
authors.initials: SC
authors.lastname: Chen
authors.affiliation: Department of Biological Chemistry, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Mohit
authors.initials: M
authors.lastname: Prasad
authors.affiliation: Department of Biological Chemistry, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Li
authors.initials: L
authors.lastname: He
authors.affiliation: Department of Biological Chemistry, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA; Université P. Sabatier Toulouse III and CNRS, LBCMCP, 31062 Toulouse Cedex 9, France.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Wang
authors.affiliation: Université P. Sabatier Toulouse III and CNRS, LBCMCP, 31062 Toulouse Cedex 9, France.
authors.forename: Valerie
authors.initials: V
authors.lastname: Choesmel-Cadamuro
authors.affiliation: Department of Biological Chemistry, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Jessica K
authors.initials: JK
authors.lastname: Sawyer
authors.affiliation: Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037-1000, USA.
authors.forename: Gaudenz
authors.initials: G
authors.lastname: Danuser
authors.affiliation: Department of Biological Chemistry, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA; Molecular, Cellular and Developmental Biology Department, University of California, Santa Barbara, Santa Barbara, CA 93106-9625, USA. Electronic address: denise.montell@lifesci.ucsb.edu.
authors.forename: Denise J
authors.initials: DJ
authors.lastname: Montell
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion; D002465:Cell Movement; D002633:Chemotaxis; D003584:Cytological Techniques; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000378:metabolism; D005260:Female; D008969:Molecular Sequence Data; D010053:Ovary / Q000166:cytology; D020744:rac GTP-Binding Proteins / Q000378:metabolism
chemical_list: D015820:Cadherins; D029721:Drosophila Proteins; C501889:shg protein, Drosophila; D020744:rac GTP-Binding Proteins