ACTIVIN COOPERATES WITH FIBROBLAST-GROWTH-FACTOR-2 TO REGULATE TYROSINE-HYDROXYLASE EXPRESSION IN THE BASAL FOREBRAIN VENTRICULAR ZONE PROGENITORS

Activin and its cognate receptors are expressed during embryogenesis i n the rapidly dividing cells of the basal forebrain ventricular zone. This finding prompted us to study the role of activin in regulating ne urotransmitter phenotype expression and other aspects of the ventricul ar zone-derived progenitor cell differentiation. although virtually in effective alone, activin co-operated with fibroblast growth factor 2 t o induce a rapid tyrosine hydroxylase-immunoreactivity in cultured ven tricular zone progenitors. Northern analysis indicated that the increa se in tyrosine hydroxylase-immunoreacrivity was associated with increa sed tyrosine hydroxylase gene expression. Activin and fibroblast growt h factor 2 action was specific to tyrosine hydroxylase, as it did not induce the expression of choline acetyltransferase, nor enhance the ex pression of glutamate decarboxylase. Cultures treated with the DNA rep lication marker bromodeoxyuridine revealed that both proliferating ven tricular zone progenitors and their post-mitotic progeny were induced to express tyrosine hydroxylase. In these cultures, activin acted to r educe fibroblast growth Factor 2 stimulated mitotic activity. Furtherm ore, activin permitted neuronal differentiation and survival of the ve ntricular zone progenitors after three days in vitro. Together these d ata demonstrate a novel role of activin and fibroblast growth factor 2 in regulating the Fate of the embryonic basal forebrain ventricular z one progenitors. (C) 1998 IBRO. Published by Elsevier Science Ltd.