Phosphotyrosine signalling as a regulator of neural crest cell adhesion and motility

We demonstrate that neural crest cell-cell adhesion, cell-substrate adhesio n, and ultimately cell motility, are highly dependent on the balanced actio n of tyrosine kinases and tyrosine phosphatases. Neural crest cell migratio n on fibronectin is diminished in the presence of the tyrosine phosphatase inhibitor vanadate or tyrosine kinase inhibitor herbimycin A, while cadheri n-rich cell-cell adhesions are significantly increased. In contrast, cells treated with the kinase inhibitor genistein have decreased motility, rearra nge rapidly and reversibly into a pavement-like monolayer, but have no incr ease in cadherin interactions. Genistein-sensitive tyrosine kinases may the refore abrogate a latent sensitivity of neural crest cells to contact-media ted inhibition of movement. Furthermore, we show that the activity of herbi mycin A-sensitive kinases is necessary for focal adhesion formation in thes e cells. Moreover, the size and distribution of these adhesions are acutely sensitive to the actions of tyrosine phosphatases and genistein-sensitive kinases. We propose that in migrating neural crest cells there is a balance in phosphotyrosine signalling which minimises both cell-cell adhesion and contact inhibition of movement, while enhancing dynamic cell-substrate inte ractions and thus the conditions for motility. (C) 1999 Wiley-Liss, Inc.