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Dev Cell. July 20, 2010; 19 (1): 39-53.

Collective chemotaxis requires contact-dependent cell polarity.

Theveneau E , Marchant L , Kuriyama S , Gull M , Moepps B , Parsons M , Mayor R .

Directional collective migration is now a widely recognized mode of migration during embryogenesis and cancer. However, how a cluster of cells responds to chemoattractants is not fully understood. Neural crest cells are among the most motile cells in the embryo, and their behavior has been likened to malignant invasion. Here, we show that neural crest cells are collectively attracted toward the chemokine Sdf1. While not involved in initially polarizing cells, Sdf1 directionally stabilizes cell protrusions promoted by cell contact. At this cell contact, N-cadherin inhibits protrusion and Rac1 activity and in turn promotes protrusions and activation of Rac1 at the free edge. These results show a role for N-cadherin during contact inhibition of locomotion, and they reveal a mechanism of chemoattraction likely to function during both embryogenesis and cancer metastasis, whereby attractants such as Sdf1 amplify and stabilize contact-dependent cell polarity, resulting in directional collective migration.

PubMed ID: 20643349
PMC ID: PMC2913244
Article link: Dev Cell.
Grant support: Biotechnology and Biological Sciences Research CouncilMedical Research CouncilWellcome Trust , G0801145 Medical Research Council , MRC_G0801145 Medical Research Council

Genes referenced: c3 cdh2 ctnnd1 cxcl12 cxcr4 psmd6 rac1 rhoa snai2 tbx2 twist1

Antibodies referenced: Ctnnb1 Ab5
Morpholinos referenced: cdh2 MO1 cxcl12 MO1

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ABERCROMBIE, 1954, Pubmed[+]

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