title: Fractone-heparan sulphates mediate FGF-2 stimulation of cell proliferation in the adult subventricular zone.
abstract: OBJECTIVE
  Fractones are extracellular matrix structures that form a niche for neural stem cells and their immediate progeny in the subventricular zone of the lateral ventricle (SVZa), the primary neurogenic zone in the adult brain. We have previously shown that heparan sulphates (HS) associated with fractones bind fibroblast growth factor-2 (FGF-2), a powerful mitotic growth factor in the SVZa. Here, our objective was to determine whether the binding of FGF-2 to fractone-HS is implicated in the mechanism leading to cell proliferation in the SVZa.
  
  
  METHODS
  Heparitinase-1 was intracerebroventricularly injected with FGF-2 to N-desulfate HS proteoglycans and determine whether the loss of HS and of FGF-2 binding to fractones modifies FGF-2 effect on cell proliferation. We also examined in vivo the binding of Alexa-Fluor-FGF-2 in relationship with the location of HS immunoreactivity in the SVZa.
  
  
  RESULTS
  Heparatinase-1 drastically reduced the stimulatory effect of FGF-2 on cell proliferation in the SVZa. Alexa-Fluor-FGF-2 binding was strictly co-localized with HS immunoreactivity in fractones and adjacent vascular basement membranes in the SVZa.
  
  
  CONCLUSIONS
  Our results demonstrate that FGF-2 requires HS to stimulate cell proliferation in the SVZa and suggest that HS associated with fractones and vascular basement membranes are responsible for activating FGF-2. Therefore, fractones and vascular basement membranes may function as a HS niche to drive cell proliferation in the adult neurogenic zone.
authors.affiliation: Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI 96822, USA.
authors.forename: V
authors.initials: V
authors.lastname: Douet
authors.forename: A
authors.initials: A
authors.lastname: Kerever
authors.forename: E
authors.initials: E
authors.lastname: Arikawa-Hirasawa
authors.forename: F
authors.initials: F
authors.lastname: Mercier
mesh_terms: D000367:Age Factors; D000818:Animals; D001485:Basement Membrane / Q000187:drug effects / Q000378:metabolism; D002452:Cell Count; D049109:Cell Proliferation; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000494:pharmacology*; D005456:Fluorescent Dyes / Q000378:metabolism; D019812:Heparan Sulfate Proteoglycans / Q000494:pharmacology; D007150:Immunohistochemistry; D020547:Lateral Ventricles / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011133:Polysaccharide-Lyases / Q000008:administration & dosage / Q000494:pharmacology; D011485:Protein Binding; D055153:Stem Cell Niche
chemical_list: D005456:Fluorescent Dyes; D019812:Heparan Sulfate Proteoglycans; D016222:Fibroblast Growth Factor 2; D011133:Polysaccharide-Lyases; C021349:heparitinsulfate lyase