Chondroitin sulfate glycosaminoglycans control proliferation, radial glia cell differentiation and neurogenesis in neural stem/progenitor cells

Abstract

Although the local environment is known to regulate neural stem cell (NSC) maintenance in the central nervous system, little is known about the molecular identity of the signals involved. Chondroitin sulfate proteoglycans (CSPGs) are enriched in the growth environment of NSCs both during development and in the adult NSC niche. In order to gather insight into potential biological roles of CSPGs for NSCs, the enzyme chondroitinase ABC (ChABC) was used to selectively degrade the CSPG glycosaminoglycans. When NSCs from mouse E13 telencephalon were cultivated as neurospheres, treatment with ChABC resulted in diminished cell proliferation and impaired neuronal differentiation, with a converse increase in astrocytes. The intrauterine injection of ChABC into the telencephalic ventricle at midneurogenesis caused a reduction in cell proliferation in the ventricular zone and a diminution of self-renewing radial glia, as revealed by the neurosphere-formation assay, and a reduction in neurogenesis. These observations suggest that CSPGs regulate neural stem/progenitor cell proliferation and intervene in fate decisions between the neuronal and glial lineage.

The extracellular matrix molecule tenascin C modulates expression levels and territories of key patterning genes during spinal cord astrocyte specification

“…We believe that Tnc and other ECM molecules promote the timely transition from an early into a late NPC. Along these lines, we recently showed that interference with glycosaminoglycan biology strongly affects cortical NPC maturation (Sirko et al, 2010;Sirko et al, 2007). In the spinal cord, the loss of Tnc leads to a sustained FGF-dependent proliferation and delayed EGF-dependent migration of immature astrocytes caused by reduced FGF signalling levels, most probably resulting from an upregulation of Sulf1.…”

“…Our laboratory has contributed to the understanding of extracellular matrix (ECM) molecules for the regulation of NPC behaviour (Czopka et al, 2010;Czopka et al, 2009;Garwood et al, 2004;Sirko et al, 2009;Sirko et al, 2010;Sirko et al, 2007;von Holst et al, 2007;von Holst et al, 2006). One particular ECM molecule is the glycoprotein tenascin C. (In this article, Tnc refers to the gene or the mRNA and Tnc refers to the protein or to general statements.)…”

Dermatan sulfotransferase Chst14/D4st1, but not chondroitin sulfotransferase Chst11/C4st1, regulates proliferation and neurogenesis of neural progenitor cells

“…CSs and DSs have important roles in neural precursor proliferation, neuronal differentiation, migration and neuroprotection (Sato et al, 2008;Sirko et al, 2007;Sugahara and Mikami, 2007;von Holst et al, 2006). Previous studies indicated that the functions of CSs and DSs on NSCs are determined by their sulfation patterns.…”

A New Role of Hindbrain Boundaries as Pools of Neural Stem/Progenitor Cells Regulated by Sox2

“…Indeed, this proteoglycan is present in several other NSC microenvironments where it was suggested for NSC survival and the maintenance of their niches [84,[125][126][127]. The rhombomere-exclusive expression of the cell surface glycoconjugate Hnk-1 may also contribute to the establishment of Sox2 negative/positive zones in the hindbrain, as in the spinal cord inhibition of Sox2 that led to ectopic expression of Hnk-1 [56].…”