Edmondson D G, Lyons G E, Martin J F, Olson E N
Department of Biochemistry and Molecular Biology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Development. 1994 May;120(5):1251-63. doi: 10.1242/dev.120.5.1251.
Members of the MEF2 family of transcription factors bind a conserved A/T-rich sequence in the control regions of many skeletal and cardiac muscle genes. To begin to assess the roles of the different Mef2 genes in the control of muscle gene expression in vivo, we analyzed by in situ hybridization the expression patterns of the Mef2a, Mef2c and Mef2d genes during mouse embryogenesis. We first detected MEF2C expression at day 7.5 postcoitum (p.c.) in cells of the cardiac mesoderm that give rise to the primitive heart tube, making MEF2C one of the earliest markers for the cardiac muscle lineage yet described. By day 8.5, MEF2A, MEF2C and MEF2D mRNAs are all detected in the myocardium. By day 9.0, MEF2C is expressed in rostral myotomes, where its expression lags by about a day behind that of myf5 and several hours behind that of myogenin. MEF2A and MEF2D are expressed at a lower level than MEF2C in the myotome at day 9.5 and are detected in more embryonic tissues than MEF2C. Expression of each of the MEF2 transcripts is observed in muscle-forming regions within the limbs at day 11.5 p.c. and within muscle fibers throughout the embryo at later developmental stages. The expression of MEF2C in the somites and fetal muscle is distinct from that of MEF2A, MEF2D and the myogenic bHLH regulatory genes, suggesting that it may represent a distinct myogenic cell type. Neural crest cells also express high levels of MEF2 mRNAs between days 8.5 and 10.5 of gestation. After day 12.5 p.c., MEF2 transcripts are detected at high levels in specific regions of the brain and ultimately in a wide range of tissues. The distinct patterns of expression of the different Mef2 genes during mouse embryogenesis suggest that these genes respond to unique developmental cues and support the notion that their products play roles in the regulation of muscle-specific transcription during establishment of the cardiac and skeletal muscle lineages.
转录因子MEF2家族的成员与许多骨骼肌和心肌基因控制区域中一个保守的富含A/T的序列结合。为了开始评估不同Mef2基因在体内控制肌肉基因表达中的作用，我们通过原位杂交分析了Mef2a、Mef2c和Mef2d基因在小鼠胚胎发育过程中的表达模式。我们首先在妊娠7.5天（p.c.）时在形成原始心管的心脏中胚层细胞中检测到MEF2C的表达，这使得MEF2C成为迄今所描述的最早的心肌谱系标记之一。到8.5天时，在心肌中检测到MEF2A、MEF2C和MEF2D的mRNA。到9.0天时，MEF2C在头侧肌节中表达，其表达比myf5落后约一天，比肌细胞生成素落后几个小时。在9.5天时，MEF2A和MEF2D在肌节中的表达水平低于MEF2C，并且在比MEF2C更多的胚胎组织中被检测到。在妊娠11.5天时，在四肢内的肌肉形成区域以及在发育后期整个胚胎的肌纤维中观察到每个MEF2转录本的表达。MEF2C在体节和胎儿肌肉中的表达与MEF2A、MEF2D以及生肌bHLH调节基因的表达不同，这表明它可能代表一种独特的生肌细胞类型。在妊娠8.5天至10.5天之间，神经嵴细胞也表达高水平的MEF2 mRNA。在妊娠12.5天之后，在大脑的特定区域以及最终在广泛的组织中检测到高水平的MEF2转录本。在小鼠胚胎发育过程中，不同Mef2基因的独特表达模式表明这些基因对独特的发育信号做出反应，并支持这样一种观点，即它们的产物在心脏和骨骼肌谱系建立过程中在肌肉特异性转录的调节中发挥作用。
