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タイトル: | Intronic delay is essential for oscillatory expression in the segmentation clock. |
著者: | Takashima, Yoshiki Ohtsuka, Toshiyuki González, Aitor Miyachi, Hitoshi Kageyama, Ryoichiro https://orcid.org/0000-0002-5985-1120 (unconfirmed) |
著者名の別形: | 影山, 龍一郎 |
キーワード: | Hes7 intronic delay negative feedback oscillation segmentation clock somitogenesis |
発行日: | 22-Feb-2011 |
出版者: | The National Academy of Sciences |
誌名: | Proceedings of the National Academy of Sciences of the United States of America |
巻: | 108 |
号: | 8 |
開始ページ: | 3300 |
終了ページ: | 3305 |
抄録: | Proper timing of gene expression is essential for many biological events, but the molecular mechanisms that control timing remain largely unclear. It has been suggested that introns contribute to the timing mechanisms of gene expression, but this hypothesis has not been tested with natural genes. One of the best systems for examining the significance of introns is the oscillator network in the somite segmentation clock, because mathematical modeling predicted that oscillating expression depends on negative feedback with a delayed timing. The basic helix-loop-helix repressor gene Hes7 is cyclically expressed in the presomitic mesoderm (PSM) and regulates the somite segmentation. Here, we found that introns lead to an ∼19-min delay in the Hes7 gene expression, and mathematical modeling suggested that without such a delay, Hes7 oscillations would be abolished. To test this prediction, we generated mice carrying the Hes7 locus whose introns were removed. In these mice, Hes7 expression did not oscillate but occurred steadily, leading to severe segmentation defects. These results indicate that introns are indeed required for Hes7 oscillations and point to the significance of intronic delays in dynamic gene expression. |
著作権等: | ©2011 by the National Academy of Sciences This is not the published version. Please cite only the published version. この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。 |
URI: | http://hdl.handle.net/2433/139496 |
DOI(出版社版): | 10.1073/pnas.1014418108 |
PubMed ID: | 21300886 |
出現コレクション: | 学術雑誌掲載論文等 |
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