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First published online 16 March 2005
doi: 10.1242/dev.01729
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1 Department of Cell and Developmental Biology, Graduate School of Biostudies,
Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan
2 Department of Molecular Oncology, Graduate School of Medicine and Dentistry,
Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo
113-8519, Japan
Author for correspondence (e-mail:
L50174{at}sakura.kudpc.kyoto-u.ac.jp)
Accepted 31 January 2005
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.
Key words: JNK, Microarray analysis, p38, Preimplantaion development, Signal transduction
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