Molecular Mechanism and Hemodynamic Function in the Outflow Tract of Heart

通过基因陷阱策略获得的隐性突变小鼠Jumonji显示出心脏缺陷。心肌小梁细胞呈高增殖状态，提示Jumonji基因下调心肌细胞的生长。Jumonj过表达的小鼠显示心脏中细胞周期蛋白D1的表达受到抑制。我们发现Jumonj蛋白与细胞周期蛋白D1启动子中的一个区域结合，并抑制启动子的活性。细胞周期蛋白D1过表达的小鼠在Jumonj突变小鼠的心脏中也观察到了同样的异常。这些结果表明，Jumonj基因通过直接抑制细胞周期蛋白D1的表达而下调心肌细胞的生长。此外，细胞周期蛋白D1是阻止心肌细胞增殖所必需的。切除鸡胚胎移植前的心脏神经脊可诱导心脏出现动脉粥样硬化。鸡胚胎心脏神经脊的消融和移植实验表明，心脏神经脊对心肌的增殖和细胞死亡具有调节作用。

The recessive mutant mouse Jumonji, obtained by a gene trap strategy, shows cardiac defects. Myocytes in the ventricular trabeculae show hyperproliferation suggesting that Jumonji gene downregulates cell growth of the cardiac myocytes. Jumonj - overexpressing mice shows repression of cyclin D1 expression in the heart. We found that Jumonj protein binds to a region in the cyclin D1 promoter and represses the promoter activity. Cyclin D1-overexpressing mice shows same abnormalities observed in the heart of Jumonj mutant mice. These results showed that Jumonj gene downregulates cell growth of the cardiac myocytes by repressing the expression of cyclin D1 directly. Furthermore, cyclin D1 is necessary for th e arrest of cardiac proliferation. Ablation of the premigrated cardiac neural crest from chick embryos induces trucus areteriosus in heart. Resulting from the ablation and transplantation experiments of the cardiac neural crest in chick embryos shows that the cardiac neural crest may regulate proliferation and cell death of myocardium.