Differential effects of SOCS2 on neuronal differentiation and morphology
Differential effects of SOCS2 on neuronal differentiation and morphology
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DOI：
10.1016/j.brainres.2005.10.032
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发表时间：
2006-01-05
期刊：
影响因子：
2.9
通讯作者：
Turnley, AM
中科院分区：
文献类型：
--
作者：
Scott, HJ;Stebbing, MJ;Turnley, AM
神经祖细胞的神经元分化受多种生长因子和转录因子的调控，这些因子不仅调控祖细胞的细胞命运，还能调控神经元的形态。细胞因子信号传导抑制因子2 （Suppressor of cytokine signaling-2, SOCS2）是生长激素（Growth Hormone， GH）信号传导的细胞内调节因子，在神经干细胞和神经元发育过程中表达，并需要克服生长激素对神经元分化的抑制作用。SOCS2也促进神经突生长，但是，SOCS2调节神经元分化和神经突生长的机制是否相同尚不清楚。此外，SOCS2的过表达是否具有生理和形态学上的影响尚不清楚。为了解决这些问题，我们分化了来自野生型CS7BL/6或SOCS2过表达转基因小鼠（SOCS2Tg）的成年神经祖细胞，并确定了生长激素存在或不存在对神经元分化和形态的影响。与野生型细胞相比，SOCS2Tg神经球的分化导致神经发生增加，而生长激素不抑制神经发生。这些细胞产生的神经元更复杂，神经突的生长和数量增加。然而，生长激素对野生型或SOCS2Tg神经元的神经突生长没有任何影响。此外，对野生型和来源于神经球的SOCS2Tg神经元的基本电生理分析表明，它们都是未成熟的电生理神经元表型，这表明尽管SOCS2表达可以调节神经元形态，但它对神经元离子通道表达的影响似乎很小。(c) 2005 Elsevier B.V.版权所有
Neuronal differentiation of neural progenitor cells is regulated by a variety of growth and transcription factors, that not only regulate cell fate of the progenitor cells but that can also regulate neuronal morphology. Suppressor of cytokine signaling-2 (SOCS2) is an intracellular regulator of Growth Hormone (GH) signaling that is expressed in neural stem cells and neurons during development and is required to overcome the inhibitory effects of GH on neuronal differentiation. SOCS2 also promotes neurite outgrowth, however, whether the mechanism by which SOCS2 regulates neuronal differentiation and neurite outgrowth is the same is not clear. Furthermore, whether the over-expression of SOCS2 has physiological in addition to morphological effects is unknown. To address these questions, we differentiated adult neural progenitor cells derived from wildtype CS7BL/6 or SOCS2 over-expressing transgenic mice (SOCS2Tg) in the presence or absence of GH and determined effects on neuronal differentiation and morphology. Compared to wildtype cells, differentiation of SOCS2Tg neurospheres resulted in increased neurogenesis, which was not inhibited by GH. The neurons derived from these cells appeared more complex, with increased neurite outgrowth and number. GH did not, however, have any effect on neurite outgrowth of wildtype or SOCS2Tg neurons. Furthermore, basic electrophysiological analysis of wildtype and SOCS2Tg neurons derived from the neurospheres showed that they were both of an immature electrophysiological neuronal phenotype, indicating that although SOCS2 expression can regulate neuronal morphology, it appears to have little effect on neuronal ion channel expression. (c) 2005 Elsevier B.V. All rights reserved.