The fully linked HTML version of this article has now been published.
Development ePress online publication date 22 Mar 2006
doi: 10.1242/dev.02344
Research article
Activation of Notch1 signaling in cardiogenic mesoderm induces abnormal heart morphogenesis in mouse
Yusuke Watanabe,
Hiroki Kokubo,
Sachiko Miyagawa-Tomita,
Maho Endo,
Katsuhide Igarashi,
Ken ichi Aisaki,
Jun Kanno,
and
Yumiko Saga*
* Author for correspondence (e-mail: ysaga{at}lab.nig.ac.jp)
Notch signaling is implicated in many developmental processes. In our current study, we have employed a transgenic strategy to investigate the role of Notch signaling during cardiac development in the mouse. Cre recombinase-mediated Notch1 (NICD1) activation in the mesodermal cell lineage leads to abnormal heart morphogenesis, which is characterized by deformities of the ventricles and atrioventricular (AV) canal. The major defects observed include impaired ventricular myocardial differentiation, the ectopic appearance of cell masses in the AV cushion, the right-shifted interventricular septum (IVS) and impaired myocardium of the AV canal. However, the fates of the endocardium and myocardium were not disrupted in NICD1-activated hearts. One of the Notch target genes, Hesr1, was found to be strongly induced in both the ventricle and the AV canal of NICD1-activated hearts. However, a knockout of the Hesr1 gene from NICD-activated hearts rescues only the abnormality of the AV myocardium. We searched for additional possible targets of NICD1 activation by GeneChip analysis and found that Wnt2, Bmp6, jagged 1 and Tnni2 are strongly upregulated in NICD1-activated hearts, and that the activation of these genes was also observed in the absence of Hesr1. Our present study thus indicates that the Notch1 signaling pathway plays a suppressive role both in AV myocardial differentiation and the maturation of the ventricular myocardium.
This article has been cited by other articles:
|
|
|
|
 
D. A. Venkatesh, K.-S. Park, A. Harrington, L. Miceli-Libby, J. K. Yoon, and L. Liaw
Cardiovascular and Hematopoietic Defects Associated With Notch1 Activation in Embryonic Tie2-Expressing Populations
Circ. Res.,
August 15, 2008;
103(4):
423 - 431.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Niessen and A. Karsan
Notch Signaling in Cardiac Development
Circ. Res.,
May 23, 2008;
102(10):
1169 - 1181.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. A. Gude, G. Emmanuel, W. Wu, C. T. Cottage, K. Fischer, P. Quijada, J. A. Muraski, R. Alvarez, M. Rubio, E. Schaefer, et al.
Activation of Notch-Mediated Protective Signaling in the Myocardium
Circ. Res.,
May 9, 2008;
102(9):
1025 - 1035.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Niessen and A. Karsan
Notch signaling in the developing cardiovascular system
Am J Physiol Cell Physiol,
July 1, 2007;
293(1):
C1 - C11.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Bolos, J. Grego-Bessa, and J. L. de la Pompa
Notch Signaling in Development and Cancer
Endocr. Rev.,
May 1, 2007;
28(3):
339 - 363.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Kokubo, S. Tomita-Miyagawa, Y. Hamada, and Y. Saga
Hesr1 and Hesr2 regulate atrioventricular boundary formation in the developing heart through the repression of Tbx2
Development,
February 15, 2007;
134(4):
747 - 755.
[Abstract]
[Full Text]
[PDF]
|
|
|
© The Company of Biologists Ltd 2006
