TY - JOUR
T1 - Mechanical feedback through E-cadherin promotes direction sensing during collective cell migration
AU - Cai, Danfeng
AU - Chen, Shann Ching
AU - Prasad, Mohit
AU - He, Li
AU - Wang, Xiaobo
AU - Choesmel-Cadamuro, Valerie
AU - Sawyer, Jessica K.
AU - Danuser, Gaudenz
AU - Montell, Denise J.
N1 - Funding Information:
We thank the D.J.M. lab for helpful discussions and Craig Montell for insightful comments on the manuscript. We thank the Erika Matunis laboratory and Bloomington Stock Center for generous sharing of fly stocks. Peter Allen produced the artwork in Figure 7 as well as the cover art. This work was supported by grants GM73164 and GM46425 (to D.J.M.), GM64346 (Cell Migration Consortium; to D.J.M. and G.D.), and GM71868 (to G.D.).
PY - 2014/5/22
Y1 - 2014/5/22
N2 - 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.
AB - 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.
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U2 - 10.1016/j.cell.2014.03.045
DO - 10.1016/j.cell.2014.03.045
M3 - Article
C2 - 24855950
AN - SCOPUS:84901317365
SN - 0092-8674
VL - 157
SP - 1146
EP - 1159
JO - Cell
JF - Cell
IS - 5
ER -