Msx1creERT2 knock-In allele: A useful tool to target embryonic and adult cardiac valves
Msx1creERT2 knock-In allele: A useful tool to target embryonic and adult cardiac valves
复制标题
DOI：
10.1002/dvg.22856
复制
发表时间：
2015-05-01
期刊：
影响因子：
1.5
通讯作者：
Zaffran, Stephane
中科院分区：
文献类型：
--
作者：
Papoutsi, Tania;Odelin, Gaelle;Zaffran, Stephane
心脏瓣膜的发育始于心内膜细胞从内皮细胞到间充质细胞的转变。尽管谱系研究表明，心脏神经嵴和心外膜分别对半月瓣和房室（AV）瓣膜形成有贡献，但大多数瓣膜间质来自心内膜EMT。用于瓣膜心内膜细胞命运定位分析的特定Cre小鼠系是有限的。在E9.5 ~ E11.5之间，EMT进行时，Msx1在房室管心内膜和缓冲间质中表达。此外，先前的研究表明Msx1及其平行Msx2的缺失会导致房室缓冲发育不良和心内膜信号传导受损。最近产生了一个敲入型他莫昔芬诱导的Cre系（Msx1(CreERT2)），并在胚胎发育和出生后进行了表征，并显示了内源性Msx1的表达模式。在这里，我们进一步分析了这个敲入等位基因，并在心脏发育过程中追踪表达msx1的细胞及其后代，特别关注它们对瓣膜及其前体的贡献。因此，Msx1（CreERT2）小鼠代表了一种有用的模型，用于心内膜和间充质缓冲细胞的谱系追踪和条件基因操作，这对了解瓣膜发育和重塑机制至关重要。创世纪53:37 -345,2015。(c) 2015 Wiley期刊公司
Heart valve development begins with the endothelial-to-mesenchymal transition (EMT) of endocardial cells. Although lineage studies have demonstrated contributions from cardiac neural crest and epicardium to semilunar and atrioventricular (AV) valve formation, respectively, most valve mesenchyme derives from the endocardial EMT. Specific Cre mouse lines for fate-mapping analyses of valve endocardial cells are limited. Msx1 displayed expression in AV canal endocardium and cushion mesenchyme between E9.5 and E11.5, when EMT is underway. Additionally, previous studies have demonstrated that deletion of Msx1 and its paralog Msx2 results in hypoplastic AV cushions and impaired endocardial signaling. A knock-in tamoxifen-inducible Cre line was recently generated (Msx1(CreERT2)) and characterized during embryonic development and after birth, and was shown to recapitulate the endogenous Msx1 expression pattern. Here, we further analyze this knock-in allele and track the Msx1-expressing cells and their descendants during cardiac development with a particular focus on their contribution to the valves and their precursors. Thus, Msx1(CreERT2) mice represent a useful model for lineage tracing and conditional gene manipulation of endocardial and mesenchymal cushion cells essential to understand mechanisms of valve development and remodeling. genesis 53:337-345, 2015. (c) 2015 Wiley Periodicals, Inc.