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observed in vitro, which includes extension of protrusions, formation of stable
attachments at the leading edge, translocation of the cell body forward, and
release at the cell rear, is recapitulated by the precursors migrating in situ.
However, unlike cultured cells, both the muscle and neuronal precursors
extended a single, long, persistent protrusion in the direction of migration, a
process regulated by Rac activation. Thus, the present cell culture systems
may not completely recapitulate the complex in vivo environment.
Introduction
Cell migration is central to many biological and pathological processes
(Lauffenburger and Horwitz, 1996) and, thus, understanding the molecular
basis of migration is of considerable importance. This is a challenging task
since migration involves the integration of several different cellular processes,
including the formation of protrusions and adhesions, translocation of the cell
body and release of adhesions at the cell rear. While many proteins that
contribute to migration have been identified, the mechanisms that regulate
some of its central processes, such as the formation and disassembly of
adhesions, are not well known. Understanding these processes should provide
significant insight into the mechanisms that regulate migration.
Most of the studies examining the molecular basis of migration have
utilized fibroblasts or tumour cells growing on tissue culture dishes. While this
is an attractive model system because of the convenience, cost and ease with
which gene expression can be manipulated, it is presently unclear how well
migration in cell culture systems mimics that seen in vivo. As mechanisms that
regulate migration emerge from in vitro studies, the next challenge is to
determine if these same mechanisms also regulate migration in vivo. The
technology to examine migration in vivo is rapidly emerging making this
formidable task possible.
Cell migration begins with the extension of the membrane in the direction of
movement. The assembly of actin filaments at the leading edge of the cell
drives the initial extension of the plasma membrane known as a protrusion
(Borisy and Svitkina, 2000; Carson et al., 1986; Wang, 1985). For migration to
occur, the protrusion must be stabilized by the formation of adhesion
complexes, which usually consist of the integrin family of transmembrane
receptors, signalling, adaptor and cytoskeletal proteins (Burridge and
Chrzanowska-Wodnicka, 1996; Schoenwaelder and Burridge, 1999; Yamada
and Miyamoto, 1995). The integrin serves as the link between the extracellular
matrix and the cytoskeleton. Rac regulates the formation of the nascent
adhesions at the cell front that drive rapid cell migration probably by serving
as traction points for the propulsive forces that move the cell body forward
(Beningo et al., 2001; Galbraith and Sheetz, 1997; Lee et al., 1994; Oliver et al.,
