Neuronal lineage‐specific induction of phospholipase Cε expression in the developing mouse brain
Neuronal lineage‐specific induction of phospholipase Cε expression in the developing mouse brain
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DOI：
10.1046/j.1460-9568.2003.02591.x
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发表时间：
2003-04
影响因子：
3.4
通讯作者：
Dongmei Wu;M. Tadano;H. Edamatsu;Misa Masago-Toda;Y. Yamawaki‐Kataoka;T. Terashima;A. Mizoguchi
中科院分区：
文献类型：
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作者：
Dongmei Wu;M. Tadano;H. Edamatsu;Misa Masago-Toda;Y. Yamawaki‐Kataoka;T. Terashima;A. Mizoguchi
磷脂酶C是中枢神经系统细胞内信号转导的关键酶。我们和其他人最近发现了一类新的磷脂酶C，磷脂酶Cε，它是由Ras和Rap小GTP酶调节。作为分析其功能的第一步，我们通过原位杂交和免疫组织化学研究了磷脂酶Cε在小鼠发育过程中的时空表达模式。在胚胎10.5天左右，磷脂酶Cε在神经管的最外层特异性表达。在胚胎第12天及以后，主要在发育中的脑和脊髓的边缘区以及经历神经元分化的其他区域（例如视网膜和嗅觉上皮）中观察到。表达磷脂酶Cε的细胞几乎总是表达微管相关蛋白2，但几乎不表达巢蛋白或胶质细胞酸性蛋白，表明磷脂酶Cε的表达在定向于神经元谱系的细胞中被特异性诱导。磷脂酶Cε在终末分化的神经元中持续表达，无区域特异性。此外，采用神经上皮干细胞的体外培养系统来显示磷脂酶Cε的丰富表达与巢蛋白表达的丧失以及微管相关蛋白2表达和神经元形态的诱导平行发生。此外，胶质细胞酸性蛋白阳性胶质细胞系细胞不表现出高磷脂酶Cε表达。这些结果表明，磷脂酶Cε表达的诱导可能是与神经前体细胞向神经元谱系的定向有关的特定事件。
Phospholipase C is a key enzyme of intracellular signal transduction in the central nervous system. We and others recently discovered a novel class of phospholipase C, phospholipase Cε, which is regulated by Ras and Rap small GTPases. As a first step toward analysis of its function, we have examined the spatial and temporal expression patterns of phospholipase Cε during mouse development by in situ hybridization and immunohistochemistry. Around embryonic day 10.5, abundant expression of phospholipase Cε is observed specifically in the outermost layer of the neural tube. On embryonic day 12 and later, it is observed mainly in the marginal zone of developing brain and spinal cord as well as in other regions undergoing neuronal differentiation, such as the retina and olfactory epithelium. The phospholipase Cε‐expressing cells almost invariably express microtubule‐associated protein 2, but hardly express nestin or glial fibrillary acidic protein, indicating that the expression of phospholipase Cε is induced specifically in cells committed to the neuronal lineage. The expression of phospholipase Cε persists in the terminally differentiated neurons and exhibits no regional specificity. Further, an in vitro culture system of neuroepithelial stem cells is employed to show that abundant expression of phospholipase Cε occurs in parallel with the loss of nestin expression as well as with the induction of microtubule‐associated protein 2 expression and neuronal morphology. Also, glial fibrillary acidic protein‐positive glial lineage cells do not exhibit the high phospholipase Cε expression. These results suggest that the induction of phospholipase Cε expression may be a specific event associated with the commitment of the neural precursor cells to the neuronal lineage.