Localization of urokinase-type plasminogen activator, its receptor, and inhibitors in mouse forebrain during postnatal development

Proteolytic enzymes are postulated to play a role in cell migration and syn apse organization during brain development. Among these, urokinase-type pla sminogen activator (uPA) has been studied in neoplastic and cultured brain cells extensively. We hypothesized that uPA, its receptor, and its inhibito rs would be expressed in immature glial and neuronal cells in postnatal mou se forebrain. Immature cortical neurons were immunoreactive for uPA, its re ceptor, and its substrate plasminogen peaking at the end of postnatal week two, consistent with the postulated role in synaptogenesis. Immunoreactivit y for uPA receptor was also observed on astroglial cells in vitro. Neither it nor uPA were convincingly detected in subventricular zone precursor cell s, immature white matter or pre-labeled immature cells that had been transp lanted into brain. Plasminogen activator inhibitor type 1 immunoreactivity was observed on endothelia up to 12 days age, and type 2 was observed to su rround immature cells. We conclude, based on the spatial and temporal distribution of immunoreacti vity, that uPA and its receptor may be relatively more important for synapt ogenesis, remodeling, and reactive processes than for cell migration in dev eloping mouse brain. (C) 1999 ISDN. Published by Elsevier Science Ltd. All rights reserved.