Mechanical feedback through E-cadherin promotes direction sensing during collective cell migration

Danfeng Cai, Shann Ching Chen, Mohit Prasad, Li He, Xiaobo Wang, Valerie Choesmel-Cadamuro, Jessica K. Sawyer, Gaudenz Danuser, Denise J. Montell

Research output: Contribution to journalArticle

238 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1146-1159
Number of pages14
JournalCell
Volume157
Issue number5
DOIs
StatePublished - May 22 2014

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Cai, D., Chen, S. C., Prasad, M., He, L., Wang, X., Choesmel-Cadamuro, V., Sawyer, J. K., Danuser, G., & Montell, D. J. (2014). Mechanical feedback through E-cadherin promotes direction sensing during collective cell migration. Cell, 157(5), 1146-1159. https://doi.org/10.1016/j.cell.2014.03.045