2010 Fiscal Year Final Research Report
New aspects of transcriptional control by Tbx5
Project/Area Number |
20370084
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Developmental biology
|
Research Institution | Tohoku University |
Principal Investigator |
OGURA Toshihiko Tohoku University, 加齢医学研究所, 教授 (60273851)
|
Project Period (FY) |
2008 – 2010
|
Keywords | TBX / MKL2 / 機械的刺激 / 心拍 / 血流 |
Research Abstract |
In the early stages of cardiac development, the genetic program regulates differentiation of cardiomyocytes and the initial morphogenesis of heart tube. However, once heartbeat commences, physical forces generated by heartbeat and/or blood circulation become an epigenetic factor that control several aspects of heart development. In this project, we have identified MKL2 as a robust co-activator for Tbx5, one of the key regulators of cardiogenesis. Interestingly, MKL2 shuttles between cytoplasm and nucleus, in a mechanical stimulus-dependent way. In zebrafish heart, MKL2 is in the cytoplasm when heartbeat is arrested, whereas it is in the nucleus in the presence of heartbeat, indicating that Tbx5 is active in the beating cardiomyocyte. In addition, pressure-overload to the left ventricle of mouse hearts also induces nuclear shuttling of Tbx5, highlighting MKL2 as a transducer of mechanical signals. To expand our knowledge on physical forces, we have identified several transcription factors that shuttle into nucleus in response to stretch and shear stresses. In addition, we also found that several miRNAs are induced in developing heart by physical forces (For example, expression of miR-21 is turned off when heartbeat is arrested, yet is rapidly and strongly induced by heartbeat.). In this project, we discovered several key force-dependent regulators of cardiogenesis, which will open a new way to explore a novel signal transduction system that is essential for development and homeostasis.
|
Research Products
(20 results)
-
-
-
-
[Journal Article] Planar polarity of multiciliated ependymal cells involves the anterior migration of basal bodies regulated by non-muscle myosin II.2010
Author(s)
Yuki Hirota, Alice Meunier, Shihhui Huang, Togo Shimozawa, Osamu Yamada, Yasuyuki S Kida, Masashi Inoue, Tsubasa Ito, Hiroko Kato, Masanori Sakaguchi, Takehiko Sunabori, Masa-aki Nakaya, Shigenori Nonaka, Toshihiko Ogura, Hideo Higuchi, Hideyuki Okano, Nathalie Spassky, Kazunobu Sawamoto
-
Journal Title
Development 137
Pages: 3037-3046
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-