Normal sulfation levels regulate spinal cord neural precursor cell proliferation and differentiation
Normal sulfation levels regulate spinal cord neural precursor cell proliferation and differentiation
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DOI：
10.1186/1749-8104-7-20
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发表时间：
2012-06-08
影响因子：
3.6
通讯作者：
Wiese, Stefan
中科院分区：
文献类型：
--
作者：
Karus, Michael;Samtleben, Samira;Wiese, Stefan
背景：硫酸化糖胺聚糖链在神经发育和再生过程中具有调节功能。然而，仍然不知道硫酸盐残基是否单独影响例如神经前体细胞行为，或者它们是否与糖骨架一起起作用。在这里，我们提供的证据表明，独特的473 HD-表位，一个代表性的硫酸软骨素，是由脊髓神经前体细胞在体内和体外表达，这表明一个潜在的功能的硫酸化糖胺聚糖脊髓development.Results：因此，我们应用广泛使用的硫酸化抑制剂氯酸钠来分析正常硫酸化水平的重要性，脊髓神经前体细胞生物学在体外。另外氯酸钠脊髓神经前体细胞培养影响细胞周期的进展，伴随着改变细胞外信号调节激酶1或2的激活水平。这导致已经处于增殖条件下的神经元的百分比更高。相反，神经胶质细胞的相对数量在很大程度上不受影响。引人注目的是，神经前体细胞衍生的神经元的形态学和电生理学特征表现出衰减的神经元成熟氯酸钠的存在下，包括干扰神经元polarization.Conclusions：总之，我们的数据表明，硫酸化是一个重要的调节神经前体细胞增殖和成熟的神经前体细胞后代在发育中的小鼠脊髓。
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.