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1 and 3 Integrins in Migrating Neural Crest Cells
Institut Jacques Monod, Centre National de la Recherche Scientifique (CNRS) et Université Paris 7-Denis Diderot, and
Laboratoire de Biologie Moléculaire et Cellulaire du Développement, CNRS et Université Pierre et Marie Curie, 75252 Paris,
France
During embryonic development, cell migration and cell differentiation are associated with dynamic modulations both in time and space of the
repertoire and function of adhesion receptors, but the
nature of the mechanisms responsible for their coordinated occurrence remains to be elucidated. Thus, migrating neural crest cells adhere to fibronectin in an integrin-dependent manner while maintaining reduced
N-cadherin-mediated intercellular contacts. In the
present study we provide evidence that, in these cells, the control of N-cadherin may rely directly on the activity of integrins involved in the process of cell motion.
Prevention of neural crest cell migration using RGD
peptides or antibodies to fibronectin and to 
1 and 3
integrins caused rapid N-cadherin-mediated cell clustering. Restoration of stable intercellular contacts resulted essentially from the recruitment of an intracellular pool of N-cadherin molecules that accumulated into
adherens junctions in tight association with the cytoskeleton and not from the redistribution of a preexisting pool of surface N-cadherin molecules. In addition, agents that cause elevation of intracellular Ca2+ after
entry across the plasma membrane were potent inhibitors of cell aggregation and reduced the N-cadherin-
mediated junctions in the cells. Finally, elevated serine/
threonine phosphorylation of catenins associated with
N-cadherin accompanied the restoration of intercellular contacts. These results indicate that, in migrating neural crest cells, 1 and 3 integrins are at the origin
of a cascade of signaling events that involve transmembrane Ca2+ fluxes, followed by activation of phosphatases and kinases, and that ultimately control the surface distribution and activity of N-cadherin. Such a
direct coupling between adhesion receptors by means
of intracellular signals may be significant for the coordinated interplay between cell-cell and cell-substratum
adhesion that occurs during embryonic development,
in wound healing, and during tumor invasion and metastasis.
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