Carmona Fontaine, C.; (2010) Directional migration of the neural crest: an interplay between contact inhibition of locomotion and co-attraction. Doctoral thesis , UCL (University College London).

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Abstract

Collective cell migration is recognised as a common feature of cell movement in vivo. Despite its importance for both morphogenesis and malignant progression, little is known about how directional and coordinated cell movements are regulated collectively. An interesting example of collective migration in vivo is the migration of Neural Crest (NC) cells. NC cells are highly migratory and multipotent embryonic cells, which migrate with remarkable directionality and coordination. In this thesis it is proposed that a mayor force in allowing NC collective directionality is given by local cell-cell interactions. Two main interactions, a repulsive and an attractive one, are identified here and their role in NC migration is analysed. First, it is shown that Contact Inhibition of Locomotion (CIL) is essential for NC migration. These cells collapse their protrusions upon contact with others and polarise towards cell-free regions leading to cell dispersion. Also, it is shown that the non-canonical Wnt signalling is crucial in this process as its members localise at the site of contact. This leads to activation of RhoA and inhibition of cell protrusions in this region. These results provide one of the rst examples of CIL in vivo and establish a novel role for non-canonical Wnt signalling. Second, a longer-range attractive interaction is also described here in a novel mechanism termed coattraction. It is shown in silico, in vitro and in vivo that when CIL is combined with coattraction, directional collective movements emerge instead of the simple dispersion allowed by CIL. Surprisingly, it was found that the anaphylatoxin/chemoattractant C3a and its receptor C3aR mediate NC coattraction. Finally, it is proposed that CIL and coattraction act together to allow cell collectives, such as the NC, to self-organise allowing a more effcient response to external signals such as chemoattractants and restrictive cues.

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