Requirement of the MAP kinase signaling pathways for mouse preimplantation development
Requirement of the MAP kinase signaling pathways for mouse preimplantation development
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DOI：
10.1242/dev.01729
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发表时间：
2005-04-01
期刊：
影响因子：
4.6
通讯作者：
Nishida, E
中科院分区：
文献类型：
--
作者：
Maekawa, M;Yamamoto, T;Nishida, E
哺乳动物植入前发育涉及几个关键事件，如致密化和囊胚形成，但对调控这一发育过程的必需基因知之甚少。在这里，我们集中在MAP激酶信号通路作为潜在的调节途径的过程。我们的研究结果表明，抑制JNK通路或p38 MAP激酶通路，但不是ERK通路，导致抑制腔的形成，JNK和p38是活跃的小鼠植入前发育。我们随后的微阵列分析显示，在分析的约39，000个转录物中，其表达水平对JNK或p38通路的抑制敏感，但对ERK通路的抑制不敏感的那些基因的数量仅为156。此外，在156个基因中，10个基因的表达（2个基因上调，8个基因下调）对JNK或p38通路的抑制敏感。这10个基因包括几个已知在轴和图案形成中起作用的基因。同时使用siRNA下调10个基因中的一些导致空腔形成异常。因此，这项研究已经成功地缩小了候选基因的兴趣，详细的分析，这可能会导致阐明植入前发育的分子机制。
Mammalian preimplantation development involves several crucial events, such as compaction and blastocyst formation, but little is known about essential genes that regulate this developmental process. Here, we have focused on MAP kinase signaling pathways as potential regulatory pathways for the process. Our results show that inhibition of the JNK pathway or of the p38 MAP kinase pathway, but not of the ERK pathway, results in inhibition of cavity formation, and that JNK and p38 are active during mouse preimplantation development. Our subsequent microarray analyses show that, of about 39,000 transcripts analyzed, the number of those genes whose expression level is sensitive to the inhibition of the JNK or the p38 pathway, but insensitive to the inhibition of the ERK pathway, is only 156. Moreover, of the 156 genes, expression of 10 genes (two genes upregulated and eight genes downregulated) is sensitive to either inhibition of the JNK or p38 pathways. These 10 genes include several genes known for their function in axis and pattern formation. Downregulation of some of the 10 genes simultaneously using siRNA leads to abnormality in cavity formation. Thus, this study has successfully narrowed down candidate genes of interest, detailed analysis of which will probably lead to elucidation of the molecular mechanism of preimplantation development.