Neudesin, a secreted factor, promotes neural cell proliferation and neuronal differentiation in mouse neural precursor cells
Neudesin, a secreted factor, promotes neural cell proliferation and neuronal differentiation in mouse neural precursor cells
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DOI：
10.1002/jnr.20849
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发表时间：
2006-06-01
影响因子：
4.2
通讯作者：
Itoh, Nobuyuki
中科院分区：
文献类型：
--
作者：
Kimura, Ikuo;Konishi, Morichika;Itoh, Nobuyuki
Neudesin在神经元中编码具有神经营养活性的分泌信号。大多数神经营养因子参与神经细胞增殖和/或分化。然而，neudesin在神经发育中的作用仍有待阐明。我们研究了neudesin在小鼠胚胎大脑皮层和培养的小鼠神经前体细胞中的表达及其在神经发育中的作用。Neudesin在发育早期的胚胎大脑皮层中表达。它的表达主要在前板，其中主要是有丝分裂后的神经细胞存在。由于neudesin mRNA在神经元出现之前在神经前体细胞中表达，因此通过使用前体细胞来检测neudesin在神经发育中的作用。Neudesin显着促进神经元分化，并推翻了未分化状态的神经前体细胞维持成纤维细胞生长因子2（FGF 2）。相反，它抑制星形胶质细胞的分化。此外，neudesin短暂促进神经细胞增殖的早期发育过程。对细胞增殖的影响与FGF 2不同，FGF 2是神经前体细胞的自我更新促进因子。分化是通过激活蛋白激酶A（PKA）和磷脂酰肌醇-3激酶（PI-3 K）途径介导的。相反，增殖是通过丝裂原活化蛋白激酶和PKA途径介导的。表达谱和活性表明neudesin在神经发育中发挥独特的作用。本研究结果揭示了neudesin在神经细胞增殖和神经元分化中的新的潜在作用。(c)2006 Wiley-Liss，Inc.
Neudesin encodes a secreted signal with neurotrophic activity in neurons. Most neurotrophic factors are involved in neural cell proliferation and/or differentiation. However, the role of neudesin in neural development remains to be elucidated. We examined the expression of neudesin in mouse embryonic cerebral cortex and cultured mouse neural precursor cells and its roles in neural development. Neudesin was expressed in the embryonic cerebral cortex early in development. Its expression was observed mainly in the preplate, where mostly postmitotic neural cells existed. Because neudesin mRNA was expressed in the neural precursor cells before the appearance of neurons, the roles of neudesin in neural development were examined by using the precursor cells. Neudesin significantly promoted neuronal differentiation and overrode the undifferentiated state of the neural precursor cells sustained by fibroblast growth factor 2 (FGF2). In contrast, it inhibited the differentiation of astrocytes. In addition, neudesin transiently promoted neural cell proliferation early in the developmental process. The effect on cell proliferation was distinct from that of FGF2, a self-renewal-promoting factor for neural precursor cells. The differentiation was mediated though activation of the protein kinase A (PKA) and phosphatidylinositol-3 kinase (PI-3K) pathways. In contrast, the proliferation was mediated through the mitogen-activated protein kinase and PKA pathways. The expression profile and activity indicate that neudesin plays unique roles in neural development. The present findings have revealed new potential roles of neudesin in neural cell proliferation and neuronal differentiation. (c) 2006 Wiley-Liss, Inc.