TISSUE-PLASMINOGEN ACTIVATOR MESSENGER-RNA EXPRESSION IN GRANULE NEURONS COINCIDES WITH THEIR MIGRATION IN THE DEVELOPING CEREBELLUM

Tissue plasminogen activator activity in the developing cerebellum, as quantified by zymography of cerebellar homogenates from embryonic day (E) 17 to adult mice, shows a peak of activity at postnatal day (P) 7 , followed by a steady 75% decrease into adulthood. Northern blot anal ysis reveals a similar pattern for tissue plasminogen activator mRNA l evels, which are low at E17 but increase dramatically, reaching their highest levels of specific mRNA/mu g RNA in P1-P7 mice and declining a bout threefold in the adult mouse. In situ hybridization of whole mous e brain sections with a tissue plasminogen activator antisense cRNA pr obe shows pronounced reactivity in the cerebellum. Although some bindi ng is associated with the cerebellar meninges, the external granule la yer is devoid of tissue plasminogen activator mRNA at all ages. Howeve r, highly labeled elongated cells, which also bind antibody to neurona l nuclear antigen and are adjacent to Bergmann glial fibers (i.e., mig rating granule neurons), are readily visible throughout the molecular and Purkinje layers at P7 and P14. In the adult mouse cerebellum, tiss ue plasminogen activator mRNA labeling is restricted to cells in the P urkinje/internal granule layers. Thus, tissue plasminogen activator ge ne expression is induced as granule neurons leave the external granule layer and begin their inward migration. (C) 1995 Wiley-Liss, Inc.