Lack of lipid phosphate phosphatase-3 in embryonic stem cells compromises neuronal differentiation and neurite outgrowth.
Lack of lipid phosphate phosphatase-3 in embryonic stem cells compromises neuronal differentiation and neurite outgrowth.
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DOI：
10.1002/dvdy.23779
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发表时间：
2012-05
影响因子：
2.5
通讯作者：
Escalante-Alcalde, Diana
中科院分区：
文献类型：
--
作者：
Sanchez-Sanchez, Roberto;Morales-Lazaro, Sara L.;Baizabal, Jose-Manuel;Sunkara, Manjula;Morris, Andrew J.;Escalante-Alcalde, Diana
溶血磷脂酸 (LPA) 和 1-磷酸鞘氨醇 (S1P) 等生物活性脂质最近被描述为 ES 细胞和神经祖细胞多能性和分化的重要调节剂。在这里，我们证明 LPP3（一种调节上述脂质水平和生物活性的酶）参与神经分化和神经突发生。我们发现 Lpp3−/− ES 细胞在体外分化为脊髓神经元，显示神经前体和年轻神经元形成的数量显着减少。此外，分化的 Lpp3−/− 神经元表现出神经突生长受损。令人惊讶的是，当 Lpp3−/− ES 细胞分化时，观察到平滑肌肌动蛋白阳性细胞的意外出现，这一事件依赖于磷酸化鞘氨醇。我们的数据表明，LPP3 在早期脊髓神经上皮发育过程中发挥着重要作用，并且它还可能有助于调节体内神经突和轴突的生长。
Bioactive lipids such as lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) have been recently described as important regulators of pluripotency and differentiation of ES cells and neural progenitors. Here we show that LPP3, an enzyme that regulates the levels and biological activities of the aforementioned lipids, participates in neural differentiation and neuritogenesis. We find that Lpp3−/− ES cells differentiated in vitro into spinal neurons, show a considerable reduction in the amount of neural precursor and young neurons formed. In addition, differentiated Lpp3−/− neurons exhibit impaired neurite outgrowth. Surprisingly, when Lpp3−/− ES cells were differentiated, an unexpected appearance of smooth muscle actin positive cells was observed, an event that was dependent upon phosphorylated sphingosines. Our data suggest that LPP3 plays a fundamental role during early spinal neuroepithelium development and that it could also be instrumental in regulating neurite and axon outgrowth in vivo.
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