ELABELA: A Hormone Essential for Heart Development Signals via the Apelin Receptor
ELABELA: A Hormone Essential for Heart Development Signals via the Apelin Receptor
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DOI：
10.1016/j.devcel.2013.11.002
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发表时间：
2013-12-23
影响因子：
11.8
通讯作者：
Reversade, Bruno
中科院分区：
文献类型：
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作者：
Chng, Serene C.;Ho, Lena;Reversade, Bruno
我们在这里报告的发现和表征的基因，ELABELA（ELA），编码32个氨基酸的保守激素。存在于人胚胎干细胞中，ELA在斑马鱼合子转录开始时表达，并且在胚胎的幼稚外胚层细胞中普遍存在。利用锌指核酸酶介导的斑马鱼基因失活，我们创建了一个等位基因系列的ela突变体。ELA无效胚胎具有受损的内胚层分化潜能，其特征在于GATA 5和SOX 17表达降低。Ela的缺失导致胚胎发育有一个基本的心脏或根本没有心脏，令人惊讶的是apelin受体（aplnr）的缺失，我们发现aplnr是Ela的同源G蛋白偶联受体。我们的研究结果揭示了肽激素ELA的存在，它与APLNR一起形成了早期心血管发育的重要信号轴。
We report here the discovery and characterization of a gene, ELABELA (ELA), encoding a conserved hormone of 32 amino acids. Present in human embryonic stem cells, ELA is expressed at the onset of zebrafish zygotic transcription and is ubiquitous in the naive ectodermal cells of the embryo. Using zinc-finger-nuclease-mediated gene inactivation in zebrafish, we created an allelic series of ela mutants. ela null embryos have impaired endoderm differentiation potential marked by reduced gata5 and sox17 expression. Loss of Ela causes embryos to develop with a rudimentary heart or no heart at all, surprisingly phenocopying the loss of the apelin receptor (aplnr), which we show serves as Ela's cognate G protein-coupled receptor. Our results reveal the existence of a peptide hormone, ELA, which, together with APLNR, forms an essential signaling axis for early cardiovascular development.