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Wnt1-Cre标记心脏神经嵴来源细胞在房室瓣分布的实验研究

Distribution of Wnt1-Cre labeled cardiac neural crest cells in atrioventricular valve
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摘要 目的心脏神经嵴细胞(CNCC)与心血管的发育密切相关,其缺陷往往导致心血管的发育畸形。然而对CNCC在心脏中的分布范围却没有统一的认识,为此探讨CNCC在心脏尤其是房室瓣的分布。方法选用12.5d胚胎和出生后2.5d、3周的小鼠为研究对象,Wnt1-Cre与Rosa26LacZ二元系统标记CNCC,X-gal染色后分析CNCC在心脏及大血管的分布。结果胚龄12.5d,小鼠流出道及其内膜垫上有大量神经嵴来源细胞,而心内膜垫处未见。出生后2.5d,神经嵴来源细胞在小鼠主、肺动脉半月瓣上广泛分布,三尖瓣处少量分布,而二尖瓣处未见蓝色细胞。在房室瓣和主动脉瓣上发现有许多黄褐色细胞。出生后3周,神经嵴来源细胞在心脏中的分布情况与2.5d时基本一致,但三尖瓣处无神经嵴来源细胞。结论 Wnt1-Cre标记神经嵴来源细胞主要参与心脏流出道的分隔,是构成大动脉半月瓣及其主动脉附属大血管的重要成分。而在房室瓣上未见分布。出生后小鼠房室瓣的黄褐色细胞,可能为黑色素细胞,但其是否来源于神经嵴细胞有待确认。 Objective Cardiac neural crest cell(CNCC)is a critical component required for cardiovascular development.Defects in CNCC could cause a spectrum of cardiovascular anomalies.However,there is no consensus on the distribution of CNCC-derived cells in heart.Here,we re-examined this issue in our mouse model.Methods We used Wnt1-Cre and Rosa26^LacZ as a binary system to genetically label CNCC and examined the distribution of CNCC-derived cells at heart in a nearly pure C57Bl6 background.Hearts were harvested at embryonic day 12.5(E12.5),postnatal day 2.5(P2.5)and 3-week old(3 weeks).X-gal staining was used to visualize Wnt1-Cre labeled CNCC.Results At E12.5,a large amount of CNCC-derived cells were found in outflow tract cushions,but not in endocardial cushion.At P2.5,we also observed abundant CNCC-derived cells in the semilunar valves of aorta and pulmonary artery,whereas only a few blue cells were spotted in the tricuspid valves and no blue cell found in the mitral valves.Interestingly,we saw many brownish cells in atrioventricular valves and aortic valves at this stage.Consistently,we observed that many blue cells contribute to the semilunar valve of great arteries in 3-week old heart,but on blue cells were found in atrioventricular valves.Conclusions Wnt1-Cre labeled CNCC-derived cells are mainly involved in the septation of cardiac outflow tract and contribute to the semilunar valves of great arteries and their major branches.No CNCC-derived cell is seen in atrioventricular valves in adult hearts.However,we noticed a large amount of brownish cells in postnatal atrioventricular valve,which are likely to be melanocytes.But whether they are derived from neural crest needs to be further verified.
作者 刘向阳 王晔 宋维亚 张臻 LIU Xiang-yang;WANG Ye;SONG Wei-ya;ZHANG Zhen(Institute for Pediatric Translational Medicine,Shanghai Children's Medical Center Affiliated to Shanghai Jiaotong University School of Medicine,Shanghai 200127,China)
出处 《中华临床医师杂志(电子版)》 CAS 2012年第22期7100-7105,共6页 Chinese Journal of Clinicians(Electronic Edition)
基金 上海市浦江计划项目(11PJ1406900) 上海高校特聘教授(东方学者)岗位计划资助
关键词 心脏流出道 神经嵴细胞 房室瓣 Wnt1-Cre R26R^LacZ Cardiac outflow tract Neural crest cell Atrioventricular valves Wnt1-Cre R26R^LacZ
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