Ras family GTPases control growth of astrocyte processes

Astrocytes in neuron-free cultures typically lack processes, although they are highly process-bearing in vivo. We show that basic fibroblast growth fa ctor (bFGF) induces cultured astrocytes to grow processes and that Ras fami ly GTPases mediate these morphological changes. Activated alleles of rac1 a nd rhoA blocked and reversed bFGF effects when introduced into astrocytes i n dissociated culture and in brain slices using recombinant adenoviruses. B y contrast, dominant negative (DN) alleles of both GTPases mimicked bFGF ef fects. A DN allele of Ha-uas blocked bFGF effects but not those of Rac1-DN or RhoA-DN. Our results show that bFGF acting through c-Ha-Ras inhibits end ogenous Rad and RhoA GTPases thereby triggering astrocyte process growth, a nd they provide evidence for the regulation of this cascade in vivo by a ye t undetermined neuron-derived factor.