Normal sulfation levels regulate spinal cord neural precursor cell proliferation and differentiation.
BACKGROUND
Sulfated glycosaminoglycan chains are known for their regulatory functions during neural development and regeneration. However, it is still unknown whether the sulfate residues alone influence, for example, neural precursor cell behavior or whether they act in concert with the sugar backbone. Here, we provide evidence that the unique 473HD-epitope, a representative chondroitin sulfate, is expressed by spinal cord neural precursor cells in vivo and in vitro, suggesting a potential function of sulfated glycosaminoglycans for spinal cord development.


RESULTS
Thus, we applied the widely used sulfation inhibitor sodium chlorate to analyze the importance of normal sulfation levels for spinal cord neural precursor cell biology in vitro. Addition of sodium chlorate to spinal cord neural precursor cell cultures affected cell cycle progression accompanied by changed extracellular signal-regulated kinase 1 or 2 activation levels. This resulted in a higher percentage of neurons already under proliferative conditions. In contrast, the relative number of glial cells was largely unaffected. Strikingly, both morphological and electrophysiological characterization of neural precursor cell-derived neurons demonstrated an attenuated neuronal maturation in the presence of sodium chlorate, including a disturbed neuronal polarization.


CONCLUSIONS
In summary, our data suggest that sulfation is an important regulator of both neural precursor cell proliferation and maturation of the neural precursor cell progeny in the developing mouse spinal cord.
Group for Molecular Cell Biology, Ruhr-University Bochum, Bochum, Germany.
Michael
M
Karus
Samira
S
Samtleben
Claudia
C
Busse
Teresa
T
Tsai
Irmgard D
ID
Dietzel
Andreas
A
Faissner
Stefan
S
Wiese
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002809:Chondroitin Sulfates / Q000378:metabolism; D005260:Female; D006025:Glycosaminoglycans / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism*; D061251:Primary Cell Culture; D013116:Spinal Cord / Q000166:cytology* / Q000196:embryology* / Q000502:physiology; D013431:Sulfates / Q000378:metabolism*
D006025:Glycosaminoglycans; D013431:Sulfates; C013786:A73025; D002809:Chondroitin Sulfates