Novel Extracellular Matrix Structures in the Neural Stem Cell Niche Capture the Neurogenic Factor FGF-2 from the Extracellular Milieu

¹ John A. Burns School of Medicine, Department of Tropical Medicine and Infectious Diseases, University of Hawaii, Honolulu, HI 96813, USA
² Jutendo University School of Medicine, Research Institute for Diseases of Old Age, Tokyo 113-3421, Japan

^* To whom correspondence should be addressed. E-mail: fmercier{at}pbrc.hawaii.edutel.

	Abstract

The novel extracellular matrix structures called fractones are found in the lateral ventricle walls, the principal adult brain stem cell niche. By electron microscopy fractones were shown to contact neural stem and progenitor cells (NSPC), suggesting a role in neurogenesis. Here, we investigated spatial relationships between proliferating NSPC and fractones, identified basic components and the first function of fractones. Using BrdU for birth-dating cells in the adult mouse lateral ventricle wall, we found most mitotic cells next to fractones, although some cells emerged next to capillaries. Like capillary basement membranes, fractones were immunoreactive for laminin 1 and 1, collagen IV, nidogen, and perlecan, but not laminin-1, in the adult rat, mouse and human. Intriguingly, N-sulfate HSPG (heparan sulfate proteoglycan) immunoreactivity was restricted to fractone subpopulations and infrequent subependymal capillaries. Double immunolabel for BrdU and N-sulfate HSPG revealed preferential mitosis next to N-sulfate HSPG immunoreactive fractones. To determine whether N sulfate HSPG immunoreactivity within fractones reflects a potential for binding neurogenic growth factors, we identified biotinylated FGF-2 binding sites in situ on frozen sections, and in vivo after intracerebroventricular injection of biotinylated FGF-2 in the adult rat or mouse. Both binding assays revealed biotinylated FGF-2 on fractone subpopulations and on infrequent subependymal capillaries. The binding of biotinylated FGF-2 was specific and dependant upon HSPG as demonstrated in vitro and in vivo by inhibition with heparatinase, and by the concomitant disappearance of N-sulfate HSPG immunoreactivity. These results strongly suggest that fractones promote growth factor activity in the neural stem cell niche.

This article has been cited by other articles:

				I. Kazanis, A. Belhadi, A. Faissner, and C. ffrench-Constant The Adult Mouse Subependymal Zone Regenerates Efficiently in the Absence of Tenascin-C J. Neurosci., December 19, 2007; 27(51): 13991 - 13996. [Abstract] [Full Text] [PDF]