Lysophosphatidic acid stimulates neuronal differentiation of cortical neuroblasts through the LPA1-Gi/o pathway
Lysophosphatidic acid stimulates neuronal differentiation of cortical neuroblasts through the LPA1-Gi/o pathway
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DOI：
10.1016/j.neuint.2006.09.008
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发表时间：
2007-01-01
影响因子：
4.2
通讯作者：
Chun, Jerold
中科院分区：
文献类型：
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作者：
Fukushima, Nobuyuki;Shano, Shinya;Chun, Jerold
溶血磷脂酸 (LPA) 是一种调节皮质发育的细胞外脂质介质。在这里，我们使用神经球培养系统研究了 LPA 如何影响皮质神经母细胞的细胞命运。我们在碱性成纤维细胞生长因子（bFGF）存在的情况下生成了神经球。在整个培养期间用 LPA 处理显着减少了神经球中的细胞数量。当来自神经球的解离单细胞通过粘附在盖玻片上诱导分化时，LPA处理的神经球中MAP2阳性神经元的比例高于单独用bFGF处理的神经球，而髓磷脂碱性蛋白阳性少突胶质细胞的比例较低。与这一发现一致，LPA 提高了神经球中 β-微管蛋白 III 型阳性年轻神经元的比例，并降低了 CD140a 阳性少突胶质细胞前体的比例。用百日咳毒素或 LPA(1) 偏好拮抗剂 Ki16425 预处理神经球可抑制 LPA 的这些作用。此外，在lpa(1)缺失小鼠的神经球中没有观察到LPA诱导的神经元分化增强。这些结果表明LPA通过LPA(1)-G(i/o)途径促进神经母细胞向神经谱系的定向。 (c) 2006 Elsevier Ltd. 保留所有权利。
Lysophosphatidic acid (LPA) is an extracellular lipid mediator that regulates cortical development. Here we examined how LPA influences the cell fate of cortical neuroblasts using a neurosphere culture system. We generated neurospheres in the presence of basic fibroblast growth factor (bFGF). Treatment with LPA throughout the culture period significantly reduced the number of cells in the neurospheres. When dissociated single cells derived from neurospheres were induced to differentiate by adherence on coverslips, the proportion of MAP2-positive neurons was higher in LPA-treated neurospheres than in those treated with bFGF alone, and the proportion of myelin basic protein-positive oligodendrocytes was lower. Consistent with this finding, LPA raised the ratio of beta-tubulin type III-positive young neurons and reduced the ratio of CD140a-positive oligodendrocyte precursors in neurospheres. These effects of LPA were inhibited by pretreatment of neurospheres with pertussis toxin or an LPA(1)-preferring antagonist, Ki16425. Moreover, LPA-induced enhancement of neuronal differentiation was not observed in neurospheres derived from lpa(1)-null mice. These results suggest that LPA promotes the commitment of neuroblasts to the neural lineage through the LPA(1)-G(i/o) pathway. (c) 2006 Elsevier Ltd. All rights reserved.