Cardiac expression of the ventricle-specific homeobox gene Irx4 is modulated by Nkx2-5 and dHand
Cardiac expression of the ventricle-specific homeobox gene Irx4 is modulated by Nkx2-5 and dHand
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DOI：
10.1006/dbio.1999.9548
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发表时间：
2000-01-15
影响因子：
2.7
通讯作者：
Seidman, CE
中科院分区：
文献类型：
--
作者：
Bruneau, BG;Bao, ZZ;Seidman, CE
我们报告的分离和鉴定的cDNA编码的小鼠和人类的同源异型盒基因，Irx 4（易洛魁同源异型盒基因4）。小鼠和人类Irx 4蛋白是高度保守的（83%），其63-aa同源结构域是超过93%的相同果蝇易洛魁图案基因。人IRX 4定位于染色体5p15.3，其与鼠染色体13同线。Irx 4转录本存在于发育中的中枢神经系统、皮肤和触须中，但主要在心室中表达。在胚胎第7.5天的小鼠中，发现Irx 4转录物存在于绒毛膜中，并且在心脏原基的离散前域中以低水平存在。在线性心管的形成及其随后的成环（E8.0-8.5）期间，Irx 4表达限于心室段，并且在心脏的后段（最终心房）和前段（最终流出道）中均不存在。在心脏腔室在形态上变得不同的所有后续阶段（E8.5-11）和进入成年期，心脏Irx 4表达仅在心室肌中发现。Irx 4基因表达也在心脏发育异常的胚胎中进行了评估：缺乏RXR α或MEF 2c的小鼠具有正常的Irx 4表达，但缺乏同源框转录因子Nkx 2 -5（Csx）的小鼠的Irx 4转录水平显着降低。dHand-null胚胎启动Irx 4表达，但不能维持正常水平。这些数据表明，同源异型盒基因Irx 4可能是心脏发育过程中心室分化的重要介导者，其位于Nkx 2 -5和dHand的下游。(C)北京大学出版社.
We report the isolation and characterization of the cDNAs encoded by the murine and human homeobox genes, Irx4 (Iroquois homeobox gene 4). Mouse and human Irx4 proteins are highly conserved (83%) and their 63-aa homeodomain is more than 93% identical to that of the Drosophila Iroquois patterning genes. Human IRX4 maps to chromosome 5p15.3, which is syntenic to murine chromosome 13. Irx4 transcripts are present in the developing central nervous system, skin, and vibrissae, but are predominantly expressed in the cardiac ventricles. In mice at embryonic day (E) 7.5, Irx4 transcripts are found in the chorion and at low levels in a discrete anterior domain of the cardiac primordia. During the formation of the linear heart tube and its subsequent looping (E8.0-8.5), Irx4 expression is restricted to the ventricular segment and is absent from both the posterior (eventual atrial) and the anterior (eventual outflow tract) segments of the heart. Throughout all subsequent stages in which the chambers of the heart become morphologically distinct (E8.5-11) and into adulthood, cardiac Irx4 expression is found exclusively in the ventricular myocardium. Irx4 gene expression was also assessed in embryos with aberrant cardiac development: mice lacking RXR alpha or MEF2c have normal Irx4 expression, but mice lacking the homeobox transcription factor Nkx2-5 (Csx) have markedly reduced levels of Irx4 transcripts. dHand-null embryos initiate Irx4 expression, but cannot maintain normal levels. These data indicate that the homeobox gene Irx4 is likely to be an important mediator of ventricular differentiation during cardiac development, which is downstream of Nkx2-5 and dHand. (C) 2000 Academic Press.