Early expression of the different isoforms of the myocyte enhancer factor-2 (MEF2) protein in myogenic as well tps non-myogenic cell lineages during mouse embryogenesis

Early expression of the different isoforms of the myocyte enhancer factor-2 (MEF2) protein in myogenic as well tps non-myogenic cell lineages during mouse embryogenesis
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DOI:
10.1016/0925-4773(96)00542-4
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发表时间:
1996-06-01
影响因子:
2.6
通讯作者:
NadalGinard, B
NadalGinard, B
中科院分区:
生物学4区
文献类型:
--
作者:
Subramanian, SV;NadalGinard, B

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MEF 2蛋白是具有肌肉特异性DNA结合活性并结合许多肌肉特异性基因的调控区中的保守的富含A/T的元件的转录因子家族。它们被认为在骨骼肌的发育和分化中具有重要作用。最近的原位杂交研究,使用小鼠MEF 2探针表明,MEF 2基因转录检测非常早期的发展在高水平的肌节和胚胎心脏的肌原细胞。然而,MEF 2A和MEF 2D转录本已在许多成体组织中检测到,在这些组织中它们不被翻译或相应的蛋白质被快速降解。因此,建立MEF 2 RNA与蛋白表达的时空相关性具有重要意义。在本研究中,我们已经进行了原位免疫组织化学的整个安装小鼠胚胎在不同的发展阶段,使用特异性的MEF 2A,MEF 2C和MEF 2D亚型的多克隆抗体。在发育的第8.5天,所有三种MEF 2亚型都在心脏中表达。MEF 2A和C在发育的第9天在吻侧最体节的少数细胞中检测到。然后,它们的表达在与体节成熟同时的喙尾方向进行。MEF 2D同种型的表达模式与MEF 2C相似,但检测到的量低得多。有趣的是,MEF 2A也早在感染后8.5天就被检测到。在胚胎脉管系统和非肌细胞中。这些结果表明,MEF 2蛋白在体节和心脏发育的早期被检测到,从而支持它们在肌发生的分级级联的早期阶段的重要性。它们在非肌肉细胞中的存在进一步表明它们也可以在确定其他中胚层衍生物(包括脉管系统细胞)中发挥作用。
MEF2 proteins are a family of transcription factors that have muscle-specific DNA binding activity and bind to conserved A/T rich elements in the regulatory regions of numerous muscle-specific genes. They are thought have an important role in the development and differentiation of skeletal muscle. Recent in situ hybridization studies using mouse MEF2 probes have shown that MEF2 gene transcripts are detected very early in development at high levels in the myogenic cells of the myotome and embryonic heart. However, MEF2A and MEF2D transcripts have been detected in many adult tissues where they are not translated or the corresponding proteins are rapidly degraded. Therefore, it is important to establsh the temporal and spatial correlation between MEF2 RNA and protein expression. In the present study we have performed in situ immunohistochemistry of whole mount mouse embryos at different stages of development using polyclonal antibodies specific for the MEF2A, MEF2C and MEF2D isoforms. At day 8.5 of development, all three MEF2 isoforms are expressed in the heart. MEF2A and C are detected in a few cells in the rostral-most somite by day 9 of development. Their expression then proceeds in a rostro-caudal direction concurrent with somite maturation. The pattern of expression of the MEF2D isoform is similar to that of MEF2C but the amount detected is much lower. Interestingly, MEF2A is also detected as early as day 8.5 p.c. in cells of the embryonic vasculature and non-myogenic cells. These results demonstrate that MEF2 proteins are detected early in development in the somites and heart, thus supporting their importance in the early stages of the hierarchical cascade of myogenesis. Their presence in non-muscle cells further suggests they could also play a role in the determination of other mesodermal derivatives, including cells of the vasculature.