Domashenko A D, Latham K E, Hatton K S
Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
Mol Reprod Dev. 1997 May;47(1):57-65. doi: 10.1002/(SICI)1098-2795(199705)47:1<57::AID-MRD8>3.0.CO;2-P.
Previous studies indicated that members of the myc gene family may be essential for preimplantation development. Other studies revealed that preimplantation embryos lacking c-myc, N-myc, or L-myc are viable, indicating that these genes are either not essential for preimplantation development or can be substituted for functionally by other myc gene family members. To investigate the possible role of these genes during preimplantation development, we determined the temporal patterns of expression of four members of the myc gene family, genes encoding myc-associated proteins, and four putative MYC target genes. We observed a sequential pattern of myc gene expression, with the L-myc mRNA expressed as a maternal transcript, the c-myc mRNA expressed during the 4-cell through morula stages, and the B-myc mRNA expressed highly at the morula and blastocysts stages. B-myc was the predominant family member expressed during preimplantation development. The mxi mRNA was not detectable and the mad mRNA was detectable only as a maternal transcript. The max mRNA, however, was expressed both as a maternal mRNA and as an embryonic message throughout most of preimplantation development. Three putative MYC target genes (Odc, cyclin E, and prothymosin-alpha) were transcriptionally induced during the 2-cell stage, and their mRNAs increased sharply in abundance during development to the morula and blastocyst stages. Another putative MYC target gene, cyclin A, was expressed both as a maternal mRNA and as an embryonic transcript. These data support the view that the expression of myc target genes may be supported initially through the expression of maternally inherited MYC proteins and corresponding mRNAs and that subsequent stage-specific changes in expression of myc genes, myc-associated genes, and myc target genes may control early differentiative events around the time of implantation.
先前的研究表明，myc基因家族的成员可能对植入前发育至关重要。其他研究显示，缺乏c-myc、N-myc或L-myc的植入前胚胎是有活力的，这表明这些基因要么对植入前发育不是必需的，要么可以在功能上被其他myc基因家族成员替代。为了研究这些基因在植入前发育过程中的可能作用，我们确定了myc基因家族的四个成员、编码与myc相关蛋白的基因以及四个假定的MYC靶基因的表达时间模式。我们观察到myc基因表达的顺序模式，L-myc mRNA作为母源转录本表达，c-myc mRNA在4细胞期至桑椹胚期表达，而B-myc mRNA在桑椹胚期和囊胚期高度表达。B-myc是植入前发育过程中表达的主要家族成员。未检测到mxi mRNA，而mad mRNA仅作为母源转录本可检测到。然而，max mRNA在整个植入前发育的大部分时间里既作为母源mRNA又作为胚胎转录本表达。三个假定的MYC靶基因（鸟氨酸脱羧酶、细胞周期蛋白E和胸腺素α原）在2细胞期被转录诱导，并且它们的mRNA在发育至桑椹胚期和囊胚期时丰度急剧增加。另一个假定的MYC靶基因，细胞周期蛋白A，既作为母源mRNA又作为胚胎转录本表达。这些数据支持这样一种观点，即myc靶基因的表达最初可能通过母源遗传的MYC蛋白和相应mRNA的表达来支持，并且随后myc基因、与myc相关基因和myc靶基因表达的阶段特异性变化可能在着床时控制早期分化事件。
