Institute of Medical Biology, Human Genetics and Embryology Laboratory, A(∗)STAR, Singapore 138648, Singapore.
Institute of Medical Biology, Human Genetics and Embryology Laboratory, A(∗)STAR, Singapore 138648, Singapore; Institute of Molecular and Cellular Biology, A(∗)STAR, Singapore 138673, Singapore; Department of Pediatrics, National University of Singapore, Singapore 119260, Singapore.
Dev Cell. 2013 Dec 23;27(6):672-80. doi: 10.1016/j.devcel.2013.11.002. Epub 2013 Dec 5.
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.
我们在此报告一个基因的发现和特征，该基因名为 ELABELA（ELA），编码一种保守的 32 个氨基酸激素。ELA 存在于人类胚胎干细胞中，在斑马鱼合子转录开始时表达，并在胚胎的原始外胚层细胞中普遍存在。我们使用锌指核酸酶介导的基因失活在斑马鱼中创建了一系列 ela 突变体等位基因。ela 缺失胚胎的内胚层分化潜力受损，gata5 和 sox17 表达减少。Ela 的缺失导致胚胎发育时心脏发育不完全或根本没有心脏，令人惊讶的是，这种表型与 Apelin 受体（aplnr）的缺失非常相似，我们证明 aplnr 是 Ela 的同源 G 蛋白偶联受体。我们的结果揭示了一种肽激素 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。
