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PLoS One January 1, 2013; 8 (12): e85717.

Cadherin-11 mediates contact inhibition of locomotion during Xenopus neural crest cell migration.

Becker SF , Mayor R , Kashef J .

Collective cell migration is an essential feature both in embryonic development and cancer progression. The molecular mechanisms of these coordinated directional cell movements still need to be elucidated. The migration of cranial neural crest (CNC) cells during embryogenesis is an excellent model for collective cell migration in vivo. These highly motile and multipotent cells migrate directionally on defined routes throughout the embryo. Interestingly, local cell-cell interactions seem to be the key force for directionality. CNC cells can change their migration direction by a repulsive cell response called contact inhibition of locomotion (CIL). Cell protrusions collapse upon homotypic cell-cell contact and internal repolarization leads to formation of new protrusions toward cell-free regions. Wnt/PCP signaling was shown to mediate activation of small RhoGTPase RhoA and inhibition of cell protrusions at the contact side. However, the mechanism how a cell recognizes the contact is poorly understood. Here, we demonstrate that Xenopus cadherin-11 (Xcad-11) mediated cell-cell adhesion is necessary in CIL for directional and collective migration of CNC cells. Reduction of Xcad-11 adhesive function resulted in higher invasiveness of CNC due to loss of CIL. Additionally, transplantation analyses revealed that CNC migratory behaviour in vivo is non-directional and incomplete when Xcad-11 adhesive function is impaired. Blocking Wnt/PCP signaling led to similar results underlining the importance of Xcad-11 in the mechanism of CIL and directional migration of CNC.

PubMed ID: 24392028
PMC ID: PMC3877381
Article link: PLoS One
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: cad cdh11 dvl1 dvl2 h2bc21 rhoa slc5a5
Morpholinos: cdh11 MO1 cdh11 MO2

Article Images: [+] show captions
References [+] :
ABERCROMBIE, The surface properties of cancer cells: a review. 1962, Pubmed