FGF-2-responsive neural stem cell proliferation requires CCg, a novel autocrine/paracrine cofactor

We have purified and characterized a factor, from the conditioned medium of neural stem cell cultures, which is required for fibroblast growth factor 2's (FGF-2) mitogenic activity on neural stem cells. This autocrine/paracri ne cofactor is a glycosylated form of cystatin C (CCg), whose N-glycosylati on is required for its activity. We further demonstrated that, both in vitr o and in vivo, neural stem cells undergoing cell division are immunopositiv e for cystatin C. Finally, we showed in vivo functional activity of CCg by demonstrating that the combined delivery of FGF-2 and CCg to the adult dent ate gyrus stimulated neurogenesis. We propose that the process of neurogene sis is controlled by the cooperation between trophic factors and autocrine/ paracrine cofactors, of which CCS is a prototype.