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胚胎小鼠心脏中肌球蛋白轻链3f转基因的区域化转录结构域:形态发生学意义

Regionalized transcriptional domains of myosin light chain 3f transgenes in the embryonic mouse heart: morphogenetic implications.

作者信息

Franco D, Kelly R, Lamers W H, Buckingham M, Moorman A F

机构信息

Department of Anatomy and Embryology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

出版信息

Dev Biol. 1997 Aug 1;188(1):17-33. doi: 10.1006/dbio.1997.8622.

Abstract

Within the embryonic heart, five segments can be distinguished: two fast-conducting atrial and ventricular compartments flanked by slow-conducting segments, the inflow tract, the atrioventricular canal, and the outflow tract. These compartments assume morphological identity as a result of looping of the linear heart tube. Subsequently, the formation of interatrial, interventricular, and outflow tract septa generates a four-chambered heart. The lack of markers that distinguish right and left compartments within the heart has prevented a precise understanding of these processes. Transgenic mice carrying an nlacZ reporter gene under transcriptional control of regulatory sequences from the MLC1F/3F gene provide specific markers to investigate such regionalization. Our results show that transgene expression is restricted to distinct regions of the myocardium: beta-galactosidase activity in 3F-nlacZ-2E mice is confined predominantly to the embryonic right atrium, atrioventricular canal, and left ventricle, whereas, in 3F-nlacZ-9 mice, the transgene is expressed in both atrial and ventricular segments (right/left) and in the atrioventricular canal, but not in the inflow and outflow tracts. These lines of mice illustrate that distinct embryonic cardiac regions have different transcriptional specificities and provide early markers of myocardial subdivisions. Regional differences in transgene expression are not detected in the linear heart tube but become apparent as the heart begins to loop. Subsequent regionalization of transgene expression provides new insights into later morphogenetic events, including the development of the atrioventricular canal and the fate of the outflow tract.

摘要

在胚胎心脏中,可以区分出五个部分:两个快速传导的心房和心室腔室,两侧是缓慢传导的部分,即流入道、房室管和流出道。由于线性心管的环化,这些腔室呈现出形态学特征。随后,房间隔、室间隔和流出道间隔的形成产生了四腔心。缺乏区分心脏左右腔室的标记物阻碍了对这些过程的精确理解。携带在MLC1F/3F基因调控序列转录控制下的nlacZ报告基因的转基因小鼠提供了用于研究这种区域化的特异性标记物。我们的结果表明,转基因表达局限于心肌的不同区域:3F-nlacZ-2E小鼠中的β-半乳糖苷酶活性主要局限于胚胎右心房、房室管和左心室,而在3F-nlacZ-9小鼠中,转基因在心房和心室段(右/左)以及房室管中表达,但在流入道和流出道中不表达。这些品系的小鼠表明,不同的胚胎心脏区域具有不同的转录特异性,并提供了心肌细分的早期标记物。转基因表达的区域差异在线性心管中未检测到,但在心脏开始环化时变得明显。随后转基因表达的区域化对后期形态发生事件提供了新的见解,包括房室管的发育和流出道的命运。

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