VARIABLE AND MULTIPLE EXPRESSION OF PROTEASE NEXIN-1 DURING MOUSE ORGANOGENESIS AND NERVOUS-SYSTEM DEVELOPMENT

Protease Nexin-1 (PN-1) also known as Glia-Derived Nexin (GDN) inhibit s the activity of several serine proteases including thrombin, tissue (tPA)- and urokinase (uPA)-type plasminogen activators. These and othe r serine proteases seem to play roles in development and tissue homeos tasis. To gain insight into where and when PN-1 might counteract serin e protease activities in vivo, we examined its mRNA and protein expres sion in the mouse embryo, postnatal developing nervous system and adul t tissues. These analyses revealed distinct temporal and spatial PN-1 expression patterns in developing cartilage, lung, skin, urogenital tr act, and central and peripheral nervous system. In the embryonic spina l cord, PN-1 expression occurs in cells lining the neural canal that a re different from the cells previously shown to express tPA. In the de veloping postnatal brain, PN-1 expression appears transiently in many neuronal cell populations. These findings suggest a role for PN-1 in t he maturation of the central nervous system, a phase that is accompani ed by the appearance of different forms of PN-1. In adults, few distin ct neuronal cell populations like pyramidal cells of the layer V in th e neocortex retained detectable levels of PN-1 expression. Also, mRNA and protein levels did not correspond in adult spleen and muscle tissu es. The widespread and complex regulation of PN-1 expression during em bryonic development and, in particular, in the early postnatal nervous system as well as in adult tissues suggests multiple roles for this s erine protease inhibitor in organogenesis and tissue homeostasis.