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/paracrine cofactor is a glycosylated form of cystatin C (CCg), whose N-glycosylation is required for its activity. We further demonstrated that, both in vitro and in vivo, neural stem cells undergoing cell division are immunopositive 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 dentate gyrus stimulated neurogenesis. We propose that the process of neurogenesis is controlled by the cooperation between trophic factors and autocrine/paracrine cofactors, of which CCg is a prototype.
Taupin
P
P
Laboratory of Genetics, The Salk Institute, La Jolla, California 92037, USA.
Ray
J
J
Fischer
W H
WH
Suhr
S T
ST
Hakansson
K
K
Grubb
A
A
Gage
F H
FH
D000818:Animals; D019898:Autocrine Communication / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000737:chemistry; D055316:Cystatin C; D015891:Cystatins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D006031:Glycosylation; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D019899:Paracrine Communication / Q000187:drug effects; D011499:Protein Processing, Post-Translational; D051381:Rats; D020539:Sequence Analysis, Protein; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
C525032:Cst3 protein, rat; D017077:Culture Media, Conditioned; D055316:Cystatin C; D015891:Cystatins; D016222:Fibroblast Growth Factor 2