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does not occur after a central lesion of the dorsal root (
Hammarberg et al.,
2000; Wallquist et al., 2004; Werner et al., 2000
). The laminin receptor,
a
7
b
1, was shown to be critical for PNS regeneration when studies using
an
a
7 knockout mouse demonstrated severely impaired regeneration follow-
ing peripheral axotomy (
Gardiner et al., 2005; Werner et al., 2000
). Interest-
ingly, in studies of
a
5 integrin, it was found that mRNA levels do not change
following peripheral injury, rather
a
5 integrin transport was enhancedwithin
adhesion complexes in extending growth cones (
Gardiner et al., 2007
). This
might appear in contrast to a study regarding cAMP, which found that
elevation did not increase the rate of tubulin transport in axons (
Han et al.,
2004
); however, there is evidence to suggest that conditioning lesions do
enhance axonal transport into peripheral axons (reviewed by
Hoffman,
2010
). Conditioned adult DRGs grown in culture grow significantly better
than unconditioned DRGs; however, when
b
1 integrin is blocked,
conditioned-induced neurite outgrowth is abolished (
Gardiner et al.,
2007
), with similar results of growth inhibition in DRGs cultured from
a
7
knockout mice (
Ekstrom et al., 2003
).
Centrally, the situation is quite static in adult CNS with integrin expression
changing little after injury. A recent study by Silver and colleagues examining
serotenergic neurons, whose axons have an increased propensity to sprout after
injury (
Inman&Steward, 2003
), showed that this class of neurons possess more
b
1 integrin on their surface than do cortical neurons, and likewise exhibit re-
duced neurite outgrowth when treated with
b
1 integrin blocking antibodies
(
Hawthorne et al., 2011
). Most other axons possess very low amounts of
integrin receptor and lack the ability to regrow following damage. In spinal
cord injury, for example, there is an upregulation of the ECM glycoprotein
tenascin-C by reactive astrocytes within and surrounding the glial scar. The
glial scar itself presents a barrier to regeneration with the increased expression
of chondroitin sulfate proteoglycans (CSPGs), but in addition to this, the lack
of the tenascin-C receptor,
a
9
b
1, further contributes to an inability for axons
to grow. In experiments by our lab, forced expression of
a
9inDRGneurons,
after dorsal root or spinal cord injury, enhanced axon regeneration through
tenascin-C-rich regions significantly above controls, however, growth did
not extend beyond the lesion site (
Andrews et al., 2009
). In response to our
modest
in vivo
results, we examined localization of integrins and found that
integrins and other transmembrane receptors (including Semaphorin
3A and TrkB) do not transport down axons
in vivo
following exogenous ex-
pression and instead remain in or near to the cell body (Melissa Andrews,
Sara Soleman, Chin-Lik Tan, Joost Verhaagen, James Fawcett, unpublished
