Lin Lizhu, Cui Li, Zhou Wenlai, Dufort Daniel, Zhang Xiaoxue, Cai Chen-Leng, Bu Lei, Yang Lei, Martin Jody, Kemler Rolf, Rosenfeld Michael G, Chen Ju, Evans Sylvia M
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Proc Natl Acad Sci U S A. 2007 May 29;104(22):9313-8. doi: 10.1073/pnas.0700923104. Epub 2007 May 22.
Recent studies have demonstrated that the LIM homeodomain transcription factor Islet1 (Isl1) marks pluripotent cardiovascular progenitor cells and is required for proliferation, survival, and migration of recently defined second heart field progenitors. Factors that are upstream of Isl1 in cardiovascular progenitors have not yet been defined. Here we demonstrate that beta-catenin is required for Isl1 expression in cardiac progenitors, directly regulating the Isl1 promoter. Ablation of beta-catenin in Isl1-expressing progenitors disrupts multiple aspects of cardiogenesis, resulting in embryonic lethality at E13. beta-Catenin is also required upstream of a number of genes required for pharyngeal arch, outflow tract, and/or atrial septal morphogenesis, including Tbx2, Tbx3, Wnt11, Shh, and Pitx2. Our findings demonstrate that beta-catenin signaling regulates proliferation and survival of cardiac progenitors.
最近的研究表明，LIM同源域转录因子胰岛1（Isl1）标记多能心血管祖细胞，并且是最近定义的第二心脏场祖细胞增殖、存活和迁移所必需的。心血管祖细胞中Isl1上游的因子尚未明确。在此，我们证明β-连环蛋白是心脏祖细胞中Isl1表达所必需的，它直接调节Isl1启动子。在表达Isl1的祖细胞中敲除β-连环蛋白会破坏心脏发生的多个方面，导致胚胎在E13期死亡。β-连环蛋白在咽弓、流出道和/或房间隔形态发生所需的许多基因上游也是必需的，包括Tbx2、Tbx3、Wnt11、Shh和Pitx2。我们的研究结果表明，β-连环蛋白信号传导调节心脏祖细胞的增殖和存活。
