MODULATED EXPRESSION OF PLASMINOGEN-ACTIVATOR SYSTEM COMPONENTS IN CULTURED-CELLS FROM DISSOCIATED MOUSE DORSAL-ROOT GANGLIA

The development and regeneration of the peripheral nervous system (PNS ) is highly dependent on the migration of Schwann cells and the extens ion of axons toward their distant targets. Plasminogen activators (PAs ) are associated with the surface of several cell types of neural orig in where they are believed to mediate localized degradation of extrace llular matrix, thus facilitating cell motility. In this study, we char acterize the expression of tissue-type (tPA) and urokinase (uPA) PAs, as well as the urokinase cell surface receptor (uPAR) during different iation of cultured cells from mouse dorsal root ganglia. During the fi rst day in culture, the mRNA levels of all three components increase f rom 75- to 163-fold, as shown using a quantitative PGR method. By 72 h r, 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 reg enerating cultures. Densitometric analysis of gel zymographs demonstra tes that the elevation in mRNA levels is accompanied by similar increa ses in the activity levels of tPA and uPA. Interestingly, in situ hybr idization 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 subpopu lations and, to a lesser extent, by Schwann cells and fibroblasts. Tak en 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.