The extracellular matrix in neural crest-cell migration

The peripheral nervous system is created by a spatiotemporally co-ordinated migratory process during which the precursor cells, the neural crest (NC) cells, transverse the embryo to reach distantly located sites. Original transplantation experiments implicated the extracellular matrix (ECM) as a pivotal factor in the regulation of this process, and subsequent in vitro and in vivo studies have uncovered a number of ECM molecules potentially responsible for the NC cell-ECM interaction. Recent genetic manipulations in mice sustain the importance of certain matrix constituents, while precluding a significant role for others and, surprisingly, for all primary integrin receptors expressed by NC cells. The gradually crystallizing paradigm envisions that guidance of the disseminating NC cells, as well as the arrest at their final tissue locations, is governed by specific 'inhibitory' ECM-associated signals. This implies that homing of peripheral neurons and their supportive cells might be dictated by a delicate equilibrium between the multiple actions of stimulatory and inhibitory molecules, which is modulated further by defined responses of the dispersing cells to these ECM components during their successive phases of phenotypic diversification.