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Cell Migration Gateway (July 2013)

Reciprocal interactions between neural crest cells and placodal cells in developing Xenopus and zebrafish embryos give rise to a ‘chase-and-run’ mode of collective migration.

The image shows migration tracks during a chase-and-run between placodes (magenta) and neural crest (cyan) in Xenopus embryos. Image courtesy of Professor Roberto Mayor, University College London, UK.

Collective cell migration is often considered in the context of just one population of cells on the move, but can often actually involve several cell types, raising obvious questions about how such mass movement is coordinated. By studying the interaction between neural crest (NC) cells and placodal cells in developing Xenopus laevis and zebrafish embryos, Eric Theveneau et al. have identified a ‘chase-and-run’ behaviour that ensures successful neural crest migration and placode segregation, and gained insight into the underlying molecular mechanisms.

The playground antics of placode cells and NC cells could be seen both in vivo and in vitro. By labelling both cell types in embryos, the researchers saw that placode cells moved randomly until NC cells arrived on the scene, at which point they ‘ran’ away, leaving gaps in the placode region. In co-culture studies, placodal cells were seen to encourage NC cells — by secreting the chemoattractant Sdf1 — to ‘chase’ them, but once the NC cells got near, the placodal cells migrated away, as they did in vivo.

This deliberate escape from the NC cells by the placode cells required transient, functional intercellular adhesion complexes to form — a glancing ‘tag’ wasn’t enough. In establishing these interfaces, the traction forces of placodal cells switched from a radial to an asymmetric distribution, becoming restricted to the free edge of the placodal cell population, which corresponded to the direction of placode movement. This came about, Theveneau et al. discovered, because N-cadherin between placode cells and at placode cell–NC cell contacts locally prevented placodal cells from adhering to the matrix and focal adhesions from maturing.

The N-cadherin-mediated physical interaction between NC cells and placodal cells also destabilized placodal cell protrusions, but for these cells to then be able to move away from the NC cells, they also needed to repolarize away from the site of cell contact, as occurs in contact inhibition of locomotion (CIL). The authors subsequently showed that the direction of movement of NC cells and placodal cells after collision was indeed biased away from the contact site, and highlighted the involvement not only of N-cadherin, but also of non-canonical Wnt/PCP signalling in this CIL and, more broadly, in the movement of placode cells away from NC cells during chase-and-run.

So, both chemotaxis and CIL are required for coordinated migration in this context, and, accordingly, inhibiting Sdf1 chemotaxis in NC cells or Wnt/PCP signalling in placode cells blocked NC migration and impaired placode segregation in developing Xenopus embryos. The data show that placodal cells tempt NC cells with a chemoattractant, but the ensuing interaction with NC cells locally inhibits cell protrusion, effectively causing the placodal cells to turn and run away. But as long as the placodal cells secrete Sdf1, the NC cells will follow, which makes this a highly effective mechanism for mediating persistent directional migration. And one which, according to Theveneau et al., might operate during the coordinated migration of different cell types from development to metastasis.

Katrin Legg - Copyright © 2013 Cell Migration Consortium

ORIGINAL RESEARCH PAPER

  1. Theveneau, E. et al. Chase-and-run between adjacent cell populations promotes directional collective migration. Nat Cell Biol., published online 16 June 2013
    doi 10.1038/ncb2772 | Article