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Sirko, S.* ; von Holst, A.* ; Weber, A.* ; Wizenmann, A. ; Theocharidis, U.* ; Götz, M. ; Faissner, A.*

Chondroitin sulfates are required for fibroblast growth factor-2-dependent proliferation and maintenance in neural stem cells and for epidermal growth factor-dependent migration of their progeny.

Stem Cells 28, 775-787 (2010)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
The neural stem cell niche of the embryonic and adult forebrain is rich in chondroitin sulfate glycosaminoglycans (CS-GAGs) that represent complex linear carbohydrate structures on the cell surface of neural stem/progenitor cells or in their intimate environment. We have reported earlier that the removal of CS-GAGs with the bacterial enzyme chondroitinase ABC (ChABC) reduced neural stem/progenitor cell proliferation and self-renewal, while this treatment favored astroglia formation at the expense of neurogenesis. Here, we studied the consequences of CS-deglycanation further and revealed that CS-GAGs are selectively required for neurosphere formation, proliferation and self-renewal of embryonic cortical neural stem/progenitor cells in response to FGF-2. Consistently, the FGF-2-dependent activation of the MAPKinase in neural stem/progenitor cells was diminished after ChABC treatment, but unaltered after EGF stimulation. Upon EGF-treatment, fewer radial glia were BLBP-positive while more were GLAST-positive after CS-GAG removal. Only in this latter situation, GLAST-positive radial glia cells extended processes that supported neuronal migration from differentiating neurospheres. CS-deglycanation also selectively increased astrocyte numbers and their migration in response to EGF. Thus, our approach revealed that CS-GAGs are essential for FGF-2-mediated proliferation and maintenance of neuron-generating neural stem/progenitor cells. Simultaneously, CS-GAGs act as a brake on the EGF-dependent maturation, migration and gliogenesis of neural stem/progenitor cells. We conclude that neural stem/progenitor cell subpopulations reside in neurospheres that are distinguishable by their responsiveness to FGF-2 and EGF that is differentially regulated by CS-carbohydrate structures.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Extracellular matrix; Proteoglycans; Self-renewal; Differentiation; Neurogenesis
ISSN (print) / ISBN 0737-1454
e-ISSN 1549-4918
Zeitschrift Stem Cells
Quellenangaben Band: 28, Heft: 4, Seiten: 775-787 Artikelnummer: , Supplement: ,
Verlag Wiley
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Stem Cell Research (ISF)