The expression of MEF2 genes is implicated in CNS neuronal differentiation

The expression of MEF2 genes is implicated in CNS neuronal differentiation
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DOI:
10.1016/s0169-328x(96)00135-0
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发表时间:
1996-12-01
期刊:
MOLECULAR BRAIN RESEARCH
影响因子:
--
通讯作者:
Bulleit, RF
Bulleit, RF
中科院分区:
其他
文献类型:
--
作者:
Lin, X;Shah, S;Bulleit, RF

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肌细胞增强因子-2(MEF2)蛋白是肌肉分化所必需的转录因子。在本研究中,我们检测了MEF2在发育中的小脑颗粒神经元中的表达。在发育中的小脑中,RNA印迹分析显示MEF2A和MEF2D的RNA水平在出生后升高。这种增加主要发生在出生后第9天左右,在出生后第15-18天达到高峰,这在成人中保持不变。这一表达过程与GABA(A)受体α(6)亚单位RNA的表达相一致,后者是成熟小脑颗粒神经元分化的标志。我们进一步观察到,使用针对MEF2A多肽产生的多克隆抗体,MEF2蛋白主要在发育中的小脑内颗粒细胞层表达。因此,随着颗粒神经元的分化和成熟,MEF2的表达增加。实验还表明,MEF2不仅在小脑中表达,而且在中枢其他区域也有表达。在成年小鼠中,MEF2亚型A、C和D的RNA表达遍及整个中枢神经系统。MEF2A和D在嗅球、海马体和小脑的表达水平最高。MEF2C在小脑和后脑的表达不同,表达水平较低。使用MEF2A多克隆抗体,我们观察到MEF2蛋白在成人中的表达模式类似,在嗅球、皮质、海马体、丘脑和小脑中高水平表达。这些观察表明,MEF2分子可能是参与中枢神经系统神经元分化的一个重要因素,类似于它们在肌肉分化中的作用。
The myocyte enhancer factor-2 (MEF2) proteins are transcription factors required for muscle differentiation. In the present study we examined MEF2 expression in developing cerebellar granule neurons. In the developing postnatal cerebellum, RNA blot analysis revealed that MEF2A and MEF2D RNA levels increase after birth. The majority of this increase occurs around postnatal day 9 reaching a peak at postnatal day 15-18 which is maintained in adults. This time course of expression coincides with the expression of GABA(A) receptor alpha(6) subunit RNA, a marker for the differentiation of the mature cerebellar granule neurons. We further observed, using the polyclonal antibody generated against an MEF2A peptide, that MEF2 protein expression occurs primarily in the internal granule cell layer of the developing cerebellum. Thus, MEF2 expression increases as granule neurons differentiate and mature. Experiments also indicated that MEF2 expression not only occurs in the cerebellum but also in other regions of the CNS. In adult mice, expression of RNA for the MEF2 isoforms A, C and D occurs throughout the CNS. MEF2A and D expression occurs at highest levels in the olfactory bulb, hippocampus and cerebellum. The expression of MEF2C differs with low levels of expression in the cerebellum and hindbrain. Using the MEF2A polyclonal antibody, we observed a similar adult pattern of expression for the MEF2 protein with high level of expression in the olfactory bulb, cortex, hippocampus, thalamus and cerebellum. These observations suggest that MEF2 molecules may be an important factor involved in CNS neuron differentiation similar to their role in muscle differentiation.