title: Perlecan is required for FGF-2 signaling in the neural stem cell niche.
abstract: In the adult subventricular zone (neurogenic niche), neural stem cells double-positive for two markers of subsets of neural stem cells in the adult central nervous system, glial fibrillary acidic protein and CD133, lie in proximity to fractones and to blood vessel basement membranes, which contain the heparan sulfate proteoglycan perlecan. Here, we demonstrate that perlecan deficiency reduces the number of both GFAP/CD133-positive neural stem cells in the subventricular zone and new neurons integrating into the olfactory bulb. We also show that FGF-2 treatment induces the expression of cyclin D2 through the activation of the Akt and Erk1/2 pathways and promotes neurosphere formation in vitro. However, in the absence of perlecan, FGF-2 fails to promote neurosphere formation. These results suggest that perlecan is a component of the neurogenic niche that regulates FGF-2 signaling and acts by promoting neural stem cell self-renewal and neurogenesis.
authors.affiliation: Research Institute for Diseases of Old Age, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Aurelien
authors.initials: A
authors.lastname: Kerever
authors.affiliation: Department of Tropical Medicine and Infectious Diseases, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, USA.
authors.forename: Frederic
authors.initials: F
authors.lastname: Mercier
authors.affiliation: Research Institute for Diseases of Old Age, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Risa
authors.initials: R
authors.lastname: Nonaka
authors.affiliation: Research Institute for Diseases of Old Age, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Susana
authors.initials: S
authors.lastname: de Vega
authors.affiliation: Research Institute for Diseases of Old Age, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Oda
authors.affiliation: Université Pierre et Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moelle Épinière (CRICM), UMRS 975, Paris, 75013 France; Inserm, U 975, Paris, 75013 France; CNRS, UMR 7225, Paris, 75013 France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Zalc
authors.affiliation: Department of Physiology and Kanrinmaru project, Keio University, School of Medicine, Shinjuku-ku, Tokyo, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Okada
authors.affiliation: Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Hattori
authors.affiliation: National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD, USA.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Yamada
authors.affiliation: Research Institute for Diseases of Old Age, Juntendo University Graduate School of Medicine, Tokyo, Japan; Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan. Electronic address: ehirasaw@juntendo.ac.jp.
authors.forename: Eri
authors.initials: E
authors.lastname: Arikawa-Hirasawa
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D019812:Heparan Sulfate Proteoglycans / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction; D055153:Stem Cell Niche / Q000187:drug effects / Q000502:physiology*
chemical_list: D019812:Heparan Sulfate Proteoglycans; D016222:Fibroblast Growth Factor 2; C071927:perlecan