title: ELABELA: a hormone essential for heart development signals via the apelin receptor.
abstract: 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.
authors: Institute of Medical Biology, Human Genetics and Embryology Laboratory, A(∗)STAR, Singapore 138648, Singapore.
authors: Serene C
authors: SC
authors: Chng
authors: Institute of Medical Biology, Human Genetics and Embryology Laboratory, A(∗)STAR, Singapore 138648, Singapore.
authors: Lena
authors: L
authors: Ho
authors: Institute of Medical Biology, Human Genetics and Embryology Laboratory, A(∗)STAR, Singapore 138648, Singapore.
authors: Jing
authors: J
authors: Tian
authors: 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. Electronic address: bruno@reversade.com.
authors: Bruno
authors: B
authors: Reversade
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D000075244:Apelin Receptors; D015153:Blotting, Western; D002454:Cell Differentiation; D000075065:Elongin; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism*; D004707:Endoderm; D018507:Gene Expression Regulation, Developmental; D005787:Gene Frequency; D006321:Heart / Q000196:embryology*; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D036361:Peptide Hormones / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*; D016335:Zinc Fingers
chemical_list: C000601133:APELA protein, human; D000075244:Apelin Receptors; D000075065:Elongin; D036361:Peptide Hormones; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D014157:Transcription Factors; D029961:Zebrafish Proteins; C519093:apelin receptor, zebrafish