Canonical Wnt signaling functions in second heart field to promote right ventricular growth

被引:151
作者
Ai, Di
Fu, Xueyao
Wang, Jun
Lu, Mei-Fang
Chen, Li
Baldini, Antonio
Klein, William H.
Martin, James F.
机构
[1] Texas A&M Hlth Sci Ctr, Inst Biosci & Technol, Houston, TX 77030 USA
[2] Univ Texas, MD Anderson Canc Ctr, Dept Biochem & Mol Biol, Unit 1000, Houston, TX 77030 USA
[3] Univ Texas, Grad Sch Biomed Sci, Training Program Genes & Dev, Houston, TX 77225 USA
[4] Baylor Coll Med, Dept Med, Program Cardiovasc Sci, Houston, TX 77030 USA
关键词
conditional genetics; cardiac progenitor; mouse; development;
D O I
10.1073/pnas.0701212104
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The second heart field (SHF), progenitor cells that are initially sequestered outside the heart, migrates into the heart and gives rise to endocardium, myocardium, and smooth muscle. Because of its distinct developmental history, the SHF is likely subjected to different signals from that of the first heart field. Previous experiments revealed that canonical Writ signaling negatively regulated first heart field speck fication. We inactivated the obligate canonical Writ effector beta-catenin using a beta-catenin conditional null allele and the Mef2c AHF cre driver that directs cre activity specifically in SHF. We also expressed a stabilized form of beta-catenin to model continuous Writ signaling in SHF. Our data indicate that Writ signaling acts in a positive fashion to promote right ventricular and interventricular myocardial expansion. Cyclin D2 and Tgf beta 2 expression was drastically reduced in beta-catenin loss-of-function mutants, indicating that Writ signaling is required for patterning and expansion of SHF derivatives. Our findings reveal that Writ signaling plays a major positive role in promoting growth and diversification of SHF precursors into right ventricular and interventricular myocardium.
引用
收藏
页码:9319 / 9324
页数:6
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