Rac1 dependent polarization triggers contact inhibition of locomotion during epithelial-to-mesenchymal transition

Contact inhibition of locomotion (CIL) was discovered more than 60 years ago, but has only recently been shown to regulate developmental migration and cell invasion in vivo. CIL is the process through which cells move away from each other after cell-cell contact. However, many cells do not exhibit CIL and instead remain in contact after cell collision and in some cases form stable junctions. To investigate what determines this behaviour, here I study neural crest (NC) cells, a migratory stem cell population whose invasive behaviour has been likened to cancer metastasis. I show that NC cells acquire CIL at the same time that they activate their Epithelial-to-Mesenchymal (EMT) program and start migrating. By comparing pre-migratory and migratory NC cells, I show that switching E- to N- cadherin during EMT is essential for CIL. I demonstrate that, before EMT, E-Cadherin exerts an inhibitory effect of on contact-dependent cell polarity via p120 and Rac1. The main function of the cadherin switch is to lift this inhibition. As a consequence, cell-cell junction breakdown observed during CIL is caused by high forces resulting from cell re-polarisation. These data provide insight into the balance of adhesion signalling that contributes to CIL in cells in vivo