Abstract
In the adult mammalian brain, new neurons are generated in a restricted region called the neurogenic niche, which refers to the specific regulatory microenvironment of neural stem cells (NSCs). Among the constituents of neurogenic niches, the extracellular matrix (ECM) has emerged as a key player in NSC maintenance, proliferation, and differentiation. In particular, heparan sulfate (HS) proteoglycans are capable of regulating various growth factor signaling pathways that influence neurogenesis. In this review, we summarize our current understanding of the ECM niche in the adult subventricular zone (SVZ), with a special focus on basement membrane (BM)-like structures called fractones, and discuss how fractones, particularly their composition of glycosaminoglycans (GAGs), may influence neurogenesis.
Highlights
In the adult mouse brain, neurogenesis occurs continuously in the subventricular zone (SVZ) of the lateral ventricle (Altman, 1963; Doetsch et al, 1997) and the subgranular zone of the hippocampal dentate gyrus (Seki and Arai, 1993; Eriksson et al, 1998)
Perlecan is present in both vascular basement membrane (BM) and fractones, and we previously reported that the presence of perlecan in fractones through its heparan sulfate (HS) chains promoted FGF-2 stimulation of neurogenesis (Kerever et al, 2014)
Minute modification of sulfation along the HS chains leads to dramatic changes in HS regulation of growth factor signaling
Summary
In the adult mouse brain, neurogenesis occurs continuously in the subventricular zone (SVZ) of the lateral ventricle (Altman, 1963; Doetsch et al, 1997) and the subgranular zone of the hippocampal dentate gyrus (Seki and Arai, 1993; Eriksson et al, 1998). Vascular BM NSCs contact a local ECM structure called fractones (Figures 1A,B). N-sulfated HS chains recognized by 10E4 epitope immunoreactivity suggests that fractones HS present higher levels of sulfation than HS from the vascular BM (Figure 1C; Kerever et al, 2007).
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