Biology Reference
In-Depth Information
1. INTRODUCTION
1.1. Integrins in the nervous system
After injury in the adult spinal cord, there is little regeneration from damaged
axons; instead, retraction bulbs form and there is limited axon sprouting
(
Bradke, Fawcett, &Spira, 2012
). This is because adult central nervous system
(CNS) axons have a low intrinsic growth capacity (
Liu, Tedeschi, Park, &He,
2011;Moore&Goldberg, 2011;Muramatsu,Ueno,&Yamashita, 2009
), and
they have to contend with inhibitory factors in their environment (
Filbin,
2003; Fitch & Silver, 2008; Gervasi, Kwok, & Fawcett, 2008; Yiu & He,
2006
). This is not the case during development; at this stage, axons have a
much greater intrinsic growth ability and grow toward their targets regulated
by extrinsic cues which provide guidance to the growth cone as it extends
over cells and through the extracellular matrix (ECM;
O'Donnell,
Chance, &Bashaw, 2009; Yu &Bargmann, 2001
). Among the molecules in-
volved in this process are the integrin family of receptors (
Denda&Reichardt,
2007
). These are cell surface proteins that bind to molecules in the ECM,
transducing extrinsic cues which regulate the cytoskeleton and activate intra-
cellular signaling pathways leading to modulation of axon growth (
Hynes,
2002; Myers, Santiago-Medina, & Gomez, 2011
).
Integrins have been implicated in axon growth both during development
and during regeneration after injury to the peripheral nervous system (PNS).
During CNS development, various integrins are expressed by numerous
neuronal populations. They are involved in axon initiation and develop-
ment (
Georges-Labouesse, Mark, Messaddeq, & Gansmuller, 1998;
Gupton & Gertler, 2010; Harper, Ye, Blong, Jacobson, & Sakaguchi,
2010; Lei et al., 2012
) and are required for the correct formation of neuronal
architecture via interactions with their ligands which are diversely expressed
throughout the CNS. There are several previous reviews on this subject
(
Clegg, Wingerd, Hikita, & Tolhurst, 2003; Denda & Reichardt, 2007;
Franco & Muller, 2011; Huber, Kolodkin, Ginty, & Cloutier, 2003;
Letourneau, Condic, & Snow, 1994; Myers et al., 2011; Reichardt &
Tomaselli, 1991; Schmid & Anton, 2003
). In the PNS, integrins have also
been implicated in axon development (
Guan, Puthenveedu, & Condic,
2003
) and additionally play a role in axon regeneration after injury
(
Gardiner et al., 2005, 2007; Vogelezang, Forster, Han, Ginsberg, &
Ffrench-Constant, 2007; Vogelezang et al., 2001; Werner et al., 2000
).
Study of integrins in the damaged adult CNS can serve two purposes.
