Verzi Michael P, McCulley David J, De Val Sarah, Dodou Evdokia, Black Brian L
Cardiovascular Research Institute, University of California, San Francisco, CA 94143-2240, USA.
Dev Biol. 2005 Nov 1;287(1):134-45. doi: 10.1016/j.ydbio.2005.08.041. Epub 2005 Sep 26.
The vertebrate heart arises from the fusion of bilateral regions of anterior mesoderm to form a linear heart tube. Recent studies in mouse and chick have demonstrated that a second cardiac progenitor population, known as the anterior or secondary heart field, is progressively added to the heart at the time of cardiac looping. While it is clear that this second field contributes to the myocardium, its precise boundaries, other lineages derived from this population, and its contributions to the postnatal heart remain unclear. In this study, we used regulatory elements from the mouse mef2c gene to direct the expression of Cre recombinase exclusively in the anterior heart field and its derivatives in transgenic mice. By crossing these mice, termed mef2c-AHF-Cre, to Cre-dependent lacZ reporter mice, we generated a fate map of the embryonic, fetal, and postnatal heart. These studies show that the endothelial and myocardial components of the outflow tract, right ventricle, and ventricular septum are derivatives of mef2c-AHF-Cre expressing cells within the anterior heart field and its derivatives. These studies also show that the atria, epicardium, coronary vessels, and the majority of outflow tract smooth muscle are not derived from this anterior heart field population. Furthermore, a transgene marker specific for the anterior heart field is expressed in the common ventricular chamber in mef2c mutant mice, suggesting that the cardiac looping defect in these mice is not due to a failure in anterior heart field addition to the heart. Finally, the Cre transgenic mice described here will be a crucial tool for conditional gene inactivation exclusively in the anterior heart field and its derivatives.
脊椎动物的心脏起源于前中胚层双侧区域的融合，形成一条线性心管。最近在小鼠和小鸡中的研究表明，在心脏发生环化时，第二个心脏祖细胞群，即所谓的前心脏场或第二心脏场，会逐渐添加到心脏中。虽然很明显这个第二心脏场对心肌有贡献，但其精确边界、源自该群体的其他谱系以及对出生后心脏的贡献仍不清楚。在本研究中，我们利用小鼠mef2c基因的调控元件，在转基因小鼠中仅在前心脏场及其衍生物中指导Cre重组酶的表达。通过将这些称为mef2c-AHF-Cre的小鼠与依赖Cre的lacZ报告基因小鼠杂交，我们生成了胚胎、胎儿和出生后心脏的命运图谱。这些研究表明，流出道、右心室和室间隔的内皮和心肌成分是前心脏场及其衍生物中表达mef2c-AHF-Cre的细胞的衍生物。这些研究还表明，心房、心外膜、冠状血管以及大部分流出道平滑肌并非源自这个前心脏场群体。此外，在前心脏场特异的转基因标记物在mef2c突变小鼠的共同心室中表达，这表明这些小鼠的心脏环化缺陷并非由于前心脏场未能添加到心脏中。最后，本文所述的Cre转基因小鼠将成为在前心脏场及其衍生物中特异性进行条件性基因失活的关键工具。
