The phenomenon of contact inhibition of cell movement (or locomotion) was first identified more than 50 years ago in fibroblast cells in vitro, and defective contact inhibition is suggested as a factor in malignant cell invasiveness. It occurs when two cells touch; they retract their protrusions and change their direction of movement. But the molecular basis of this inhibition, and whether it happens in vivo, are still matters of controversy. Now time-lapse microscopy of neural crest cells, highly migratory cells of embryonic origin, has been used to demonstrate contact inhibition of locomotion both in vivo and in vitro, and that it can account for their directional migration. But when a neural crest cell meets another cell type it fails to display contact inhibition of locomotion, allowing it to invade the tissue. This paper studies a phenomenon called contact inhibition of locomotion, whereby fibroblast cells grown in cell culture retract their protrusions and change their direction on contact. It is shown that this occurs in vivo, and the molecular basis is revealed. Neural crest cells, highly migratory cells of embryonic origin, exhibit contact inhibition of locomotion both in vivo and in vitro, which accounts for their directional migration. However, when a neural crest cell meets another cell type, it fails to display contact inhibition of locomotion, allowing it to invade the tissue. Contact inhibition of locomotion was discovered by Abercrombie more than 50 years ago and describes the behaviour of fibroblast cells confronting each other in vitro, where they retract their protrusions and change direction on contact1,2. Its failure was suggested to contribute to malignant invasion3,4,5,6. However, the molecular basis of contact inhibition of locomotion and whether it also occurs in vivo are still unknown. Here we show that neural crest cells, a highly migratory and multipotent embryonic cell population, whose behaviour has been likened to malignant invasion6,7,8, demonstrate contact inhibition of locomotion both in vivo and in vitro, and that this accounts for their directional migration. When two migrating neural crest cells meet, they stop, collapse their protrusions and change direction. In contrast, when a neural crest cell meets another cell type, it fails to display contact inhibition of locomotion; instead, it invades the other tissue, in the same manner as metastatic cancer cells3,5,9. We show that inhibition of non-canonical Wnt signalling abolishes both contact inhibition of locomotion and the directionality of neural crest migration. Wnt-signalling members localize at the site of cell contact, leading to activation of RhoA in this region. These results provide the first example of contact inhibition of locomotion in vivo, provide an explanation for coherent directional migration of groups of cells and establish a previously unknown role for non-canonical Wnt signalling.

During neural induction, the embryonic neural plate is specified and set aside from other parts of the ectoderm. A popular molecular explanation is the`default model' of neural induction, which proposes that ectodermal cells give rise to neural plate if they receive no signals at all, while BMP activity directs them to become epidermis. However, neural induction now appears to be more complex than once thought, and can no longer be fully explained by the default model alone. This review summarizes neural induction events in different species and highlights some unanswered questions about this important developmental process.