Connexin 43 expression reflects neural crest patterns during cardiovascular development.
Connexin 43 expression reflects neural crest patterns during cardiovascular development.
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DOI：
10.1006/dbio.1999.9219
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发表时间：
1999-04
影响因子：
2.7
通讯作者：
K. Waldo;C. Lo;M. Kirby
中科院分区：
文献类型：
--
作者：
K. Waldo;C. Lo;M. Kirby
我们使用连接蛋白43的启动子序列连接到LacZ报告基因的转基因小鼠，在神经脊细胞中表达，而不是在心肌细胞中表达，以证明心脏神经脊细胞在尾咽弓和心脏流出道中的模式。LacZ的表达与鹌鹑-雏鸡嵌合体心脏神经脊细胞的表达非常相似。通过使用这个转基因小鼠品系来比较心脏神经脊在小鼠和鸡的心脏流出道隔和主动脉弓动脉发育中的作用，我们能够注意到它们在心血管发育方面的差异和相似之处。与雏鸡的神经脊细胞相似，LacZ阳性细胞在永存的主动脉弓动脉周围形成鞘，构成主-肺间隔复合体，位于锥状体垫的最终融合部位，分布于心脏神经节。在这项研究中产生的鹌鹑-雏鸡嵌合体中，神经脊细胞通过两条途径进入流出道，心肌下和心内膜下。在小鼠中，当细胞进入流出道时，只能看到心内膜下的LacZ阳性细胞群。此外，在分离前，LacZ阳性细胞完全包围了主动脉囊，而在雏鸡中，神经脊细胞散布在主动脉囊周围，大部分细胞分布在主-肺间隔复合体的桥接部。在雏鸡中，心肌下神经脊细胞聚集在主动脉囊的两侧，进入圆锥干脊。尽管小鼠的主动脉囊最初被LacZ阳性细胞包围，但由于其间隔而导致的两条流出血管显示出不同的LacZ表达。升主动脉被LacZ阳性细胞包裹，而肺动脉干无LacZ染色。在雏鸡中，这两条血管都是由神经脊细胞包裹的，但在血管延长过程中，这些细胞通过移位从主动脉弓动脉到达。这可能表明小鼠肺干来源的不同，或心脏神经脊细胞分布的不同。需要一个独立的小鼠神经脊标记来确认这种差异是否确实是由于心血管和/或神经脊发育的物种差异所致。尽管如此，由于注意到了差异，我们认为这个小鼠模型忠实地代表了心脏神经脊细胞的位置。表达LacZ的细胞在小鼠体内的位置与鸡的心脏神经脊细胞的位置相似，这表明该小鼠是研究哺乳动物心脏神经脊的良好模型，哺乳动物心脏神经脊的功能与鸡的相似。
We used transgenic mice in which the promoter sequence for connexin 43 linked to a lacZ reporter was expressed in neural crest but not myocardial cells to document the pattern of cardiac neural crest cells in the caudal pharyngeal arches and cardiac outflow tract. Expression of lacZ was strikingly similar to that of cardiac neural crest cells in quail-chick chimeras. By using this transgenic mouse line to compare cardiac neural crest involvement in cardiac outflow septation and aortic arch artery development in mouse and chick, we were able to note differences and similarities in their cardiovascular development. Similar to neural crest cells in the chick, lacZ-positive cells formed a sheath around the persisting aortic arch arteries, comprised the aorticopulmonary septation complex, were located at the site of final fusion of the conal cushions, and populated the cardiac ganglia. In quail-chick chimeras generated for this study, neural crest cells entered the outflow tract by two pathways, submyocardially and subendocardially. In the mouse only the subendocardial population of lacZ-positive cells could be seen as the cells entered the outflow tract. In addition lacZ-positive cells completely surrounded the aortic sac prior to septation, while in the chick, neural crest cells were scattered around the aortic sac with the bulk of cells distributed in the bridging portion of the aorticopulmonary septation complex. In the chick, submyocardial populations of neural crest cells assembled on opposite sides of the aortic sac and entered the conotruncal ridges. Even though the aortic sac in the mouse was initially surrounded by lacZ-positive cells, the two outflow vessels that resulted from its septation showed differential lacZ expression. The ascending aorta was invested by lacZ-positive cells while the pulmonary trunk was devoid of lacZ staining. In the chick, both of these vessels were invested by neural crest cells, but the cells arrived secondarily by displacement from the aortic arch arteries during vessel elongation. This may indicate a difference in derivation of the pulmonary trunk in the mouse or a difference in distribution of cardiac neural crest cells. An independent mouse neural crest marker is needed to confirm whether the differences are indeed due to species differences in cardiovascular and/or neural crest development. Nevertheless, with the differences noted, we believe that this mouse model faithfully represents the location of cardiac neural crest cells. The similarities in location of lacZ-expressing cells in the mouse to that of cardiac neural crest cells in the chick suggest that this mouse is a good model for studying mammalian cardiac neural crest and that the mammalian cardiac neural crest performs functions similar to those shown for chick.