Role of the extracellular matrix during neural crest cell migration

Once specified to become neural crest (NC), cells occupying the dorsal port ion of the neural tube disrupt their cadherin-mediated cell-cell contacts, acquire motile properties, and embark upon an extensive migration through t he embryo to reach their ultimate phenotype-specific sites. The understandi ng of how this movement is regulated is still rather fragmentary due to the complexity of the cellular and molecular interactions involved. An additio nal intricate aspect of the regulation of NC cell movement is that the timi ngs, modes and patterns of NC cell migration are intimately associated with the concomitant phenotypic diversification that cells undergo during their migratory phase and the fact that these changes modulate the way that movi ng cells interact with their microenvironment. To date, two interplaying me chanisms appear central for the guidance of the migrating NC cells through the embryo: one involves secreted signalling molecules acting through their cognate protein kinase/phosphatase-type receptors and the other is contrib uted by the multivalent interactions of the cells with their surrounding ex tracellular matrix (ECM). The latter ones seem fundamental in light of the central morphogenetic role played by the intracellular signals transduced t hrough the cytoscheleton upon integrin ligation, and the convergence of the se signalling cascades with those triggered by cadherins, survival/growth f actor receptors, gap junctional communications, and stretch-activated calci um channels. The elucidation of the importance of the ECM during NC cell mo vement is presently favoured by the augmenting knowledge about the macromol ecular structure of the specific ECM assembled during NC development and th e functional assaying of its individual constituents via molecular and gene tic manipulations. Collectively, these data propose that NC cell migration may be governed by time- and space-dependent alterations in the expression of inhibitory ECM components; the relative ratio of permissive versus non-p ermissive ECM components; and the supramolecular assembly of permissive ECM components. Six multidomain ECM constituents encoded by a corresponding nu mber of genes appear to date the master ECM molecules in the control of NC cell movement. These are fibronectin, laminin isoforms 1 and 8, aggrecan, a nd PG-M/version isoforms V0 and V1. This review revisits a number of origin al observations in amphibian and avian embryos and discusses them in light of more recent experimental data to explain how the interaction of moving N C cells with these ECM components maybe coordinated to guide cells toward t heir final sites during the process of organogenesis. (C) 2000 Elsevier Sci ence Ireland Ltd. All rights reserved.