Calcium receptor expression and function in oligodendrocyte commitment and lineage progression: Potential impact on reduced myelin basic protein in CaR-null mice
Calcium receptor expression and function in oligodendrocyte commitment and lineage progression: Potential impact on reduced myelin basic protein in CaR-null mice
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DOI：
10.1002/jnr.21662
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发表时间：
2008-08-01
影响因子：
4.2
通讯作者：
de Vellis, Jean
中科院分区：
文献类型：
--
作者：
Chattopadhyay, Naibedya;Espinosa-Jeffrey, Araceli;de Vellis, Jean
少突胶质细胞由少突胶质前体细胞(OPC)发育而来，少突胶质前体细胞(OPC)在中期神经发生过程中又起源于神经上皮前体细胞亚群。少突胶质细胞谱系的发育涉及过多的细胞内、外信号。细胞表面钙敏感受体(CAR)在未成熟的寡树突状细胞中有功能性表达。在这里，我们研究了CAR在少突胶质细胞发育过程中的表达和功能。我们发现，定量聚合酶链式反应评估的CAR基因表达的顺序是成熟少突胶质细胞&神经元&星形胶质细胞。接下来，我们确定了诱导特定神经干细胞向神经元、少突胶质细胞或星形胶质细胞分化的CAR表达的等级顺序，发现CAR mRNA的相对表达水平是OPC>；神经元>；星形胶质细胞。在沿着少突胶质细胞谱系发育的不同阶段的细胞中，CAR mRNA的表达表明，其表达在OPC阶段强烈上调，并在髓鞘前期保持高水平，此后在成熟的少突胶质细胞中下降数倍。在OPC中，高钙通过CAR作用促进细胞增殖。我们进一步观察到，高钙刺激前少突胶质细胞髓鞘碱性蛋白的mRNA水平，这也是CAR介导的。最后，在发育过程中，CAR缺失型小鼠小脑中髓鞘碱性蛋白水平显著降低。我们的结果表明，当神经干细胞被指定为少突胶质细胞谱系时，CAR的表达上调，并且受体的激活导致OPC的扩张和分化。我们的结论是，CAR可能是一种新的少突胶质细胞发育和功能调节因子。(C)2008年Wiley-Liss，Inc.
Oligodendrocytes develop from oligodendrocyte progenitor cells (OPCs), which in turn arise from a subset of neuroepithelial precursor cells during midneurogenesis. Development of the oligodendrocyte lineage involves a plethora of cell-intrinsic and -extrinsic signals. A cell surface calcium-sensing receptor (CaR) has been shown to be functionally expressed in immature oligo-dendrocytes. Here, we investigated the expression and function of the CaR during oligodendrocyte development. We show that the order of CaR mRNA expression as assessed by quantitative polymerase chain reaction is mature oligodendrocyte > neuron > astrocyte. We next determined the rank order of CaR expression on inducing specification of neural stem cells to the neuronal, oligodendroglial, or astrocytic lineages and found that the relative levels of CaR mRNA expression are OPC > neuron > astrocytes. CaR mRNA expression in cells at various stages of development along the oligodendrocyte lineage revealed that its expression is robustly up-regulated during the OPC stage and remains high until the premyelinating stage, decreasing thereafter by severalfold in the mature oligodendrocyte. In OPCs, high Ca2+ acting via the CaR promotes cellular proliferation. We further observed that high Ca2+ stimulates the mRNA levels of myelin basic protein in preoligodendrocytes, which is also CaR mediated. Finally, myelin basic protein levels were significantly reduced in the cerebellum of CaR-null mice during development. Our results show that CaR expression is up-regulated when neural stem cells are specified to the oligodendrocyte lineage and that activation of the receptor results in OPC expansion and differentiation. We conclude that the CaR may be a novel regulator of oligodendroglial development and function. (c) 2008 Wiley-Liss, Inc.