Heart of glass regulates the concentric growth of the heart in zebrafish
Heart of glass regulates the concentric growth of the heart in zebrafish
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DOI：
10.1016/j.cub.2003.11.055
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发表时间：
2003-12-16
期刊：
影响因子：
9.2
通讯作者：
Fishman, MC
中科院分区：
文献类型：
--
作者：
Mably, JD;Mohideen, MAPK;Fishman, MC
背景：脊椎动物器官的模式生长对于正常的生理功能是必不可少的，但控制器官类型生长的潜在途径尚不清楚。心脏功能严重依赖于室壁的同心性增厚，这是由细胞沿心内膜(心内膜)到腔室外的轴向心肌细胞的增加而产生的。在玻璃突变胚胎的心脏中，心肌细胞数量正常，但它们不是沿同心方向增加的。结果：为了确定控制心肌细胞向心性生长的因素，我们采用定位克隆的方法鉴定了玻璃心脏(HEG)基因。HEG编码一种功能未知的蛋白质，在心脏的心内膜层表达。通过选择性剪接，产生了三种不同的亚型，其中一种被预测为跨膜，另外两种被预测为分泌型。通过选择性的吗啉微扰，我们证明了跨膜形式对于正常的生长模式是关键的。结论：玻璃心脏编码了一个以前没有特征的心内膜信号，这对于形成心脏的同心性生长模式至关重要。心脏的生长需要沿心内膜到心肌轴的心肌细胞的增加。这个图案轴是由HEG驱动的，HEG是一种在心内膜表达的新的跨膜蛋白。
Background: Patterned growth of vertebrate organs is essential for normal physiological function, but the underlying pathways that govern organotypic growth are not clearly understood. Heart function is critically dependent upon the concentric thickening of the ventricular wall generated by the addition of cells to the myocardium along the axis from the endocardium (inside) to the outside of the chamber. In heart of glass mutant embryos, the number of cells in the myocardium is normal, but they are not added in the concentric direction. As a consequence, the chambers are huge and dysfunctional, and the myocardium remains a single layer.Results: To begin to define the factors controlling the concentric growth of cells in the myocardium, we used positional cloning to identify the heart of glass (heg) gene. heg encodes a protein of previously undescribed function, expressed in the endocardial layer of the heart. By alternative splicing, three distinct isoforms are generated, one of which is predicted to be transmembrane and two other secreted. By selective morpholino perturbation, we demonstrate that the transmembrane form is critical for the normal pattern of growth.Conclusions: heart of glass encodes a previously uncharacterized endocardial signal that is vital for patterning concentric growth of the heart. Growth of the heart requires addition of myocardial cells along the endocardial-to-myocardial axis. This axis of patterning is driven by heg, a novel transmembrane protein expressed in the endocardium.