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Journal of Neuroscience, Vol 16, 2307-2317, Copyright © 1996 by Society for Neuroscience
Modulated expression of plasminogen activator system components in cultured cells from dissociated mouse dorsal root ganglia
SM Hayden and NW Seeds
Neuroscience Program, University of Colorado Health Sciences Center, Denver, 80262, USA.
The development and regeneration of the peripheral nervous system (PNS) is
highly dependent on the migration of Schwann cells and the extension of
axons toward their distant targets. Plasminogen activators (PAs) are
associated with the surface of several cell types of neural origin where
they are believed to mediate localized degradation of extracellular matrix,
thus facilitating cell motility. In this study, we characterize the
expression of tissue-type (tPA) and urokinase (uPA) PAs, as well as the
urokinase cell surface receptor (uPAR) during differentiation of cultured
cells from mouse dorsal root ganglia. During the first day in culture, the
mRNA levels of all three components increase from 75- to 163-fold, as shown
using a quantitative PCR method. By 72 hr, the mRNA levels decrease and
approach basal levels. This transient increase is in direct correlation
with the differentiation of neurons and Schwann cells and the formation of
a neuritic network in these regenerating cultures. Densitometric analysis
of gel zymographs demonstrates that the elevation in mRNA levels is
accompanied by similar increases in the activity levels of tPA and uPA.
Interestingly, in situ hybridization studies of the cultures show that tPA
mRNA is restricted to small sensory neurons, whereas uPA mRNA is localized
predominantly in large sensory neurons. uPAR mRNA is expressed by both
neuronal subpopulations and, to a lesser extent, by Schwann cells and
fibroblasts. Taken together, these results further support a role for the
PA system in facilitating axon extension and cell migration during
development and regeneration of the PNS.
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