Biology Reference
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19
Regulation of Cell Migration
In Vitro and In Vivo
Donna J. Webb, Karen Donais, Shin-ichi Murase,
Hannelore Asmussen and Alan F. Horwitz
Understanding migration is challenging because it involves the integration of
many different processes that occur in distinct locations in the cell.
Considerable progress has been made in identifying molecules that contribute
to migration, but the mechanisms that regulate its central processes, such as
formation and disassembly of adhesions, remain largely unknown. As
mechanisms that regulate migration emerge from in vitro studies, the next
challenge is to determine whether these same mechanisms also regulate
migration in vivo. We have developed assays to gain insight into these
processes both in vitro and in vivo, which is the focus of this overview. To
address the mechanisms of adhesion formation and disassembly, we visualize
the dynamics of adhesion molecules fused to GFP in migrating cells. FAK,
paxillin and zyxin localized in small clusters near the leading edge of the cell.
The adhesions at the base of a protrusion disappear as new adhesions form
near the leading edge, which we refer to as adhesion turnover. FAK and Src
activity regulate turnover of these nascent adhesions at the cell front. In
addition, FAK plays a role in the disassembly of adhesions at the rear of the
cell. We then asked whether the same mechanisms regulate migration in vitro
and in vivo. To address this, we are developing in situ migration systems that
closely mimic the in vivo environment. To date, these include migration of
muscle precursors from somites to the limb bud and migration of neuronal
precursors in the rostral migratory stream (RMS). The basic migratory cycle
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