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Dev Cell. 2013 Dec 23;27(6):672-80. doi: 10.1016/j.devcel.2013.11.002. Epub 2013 Dec 5.

ELABELA: a hormone essential for heart development signals via the apelin receptor.

Author information

1
Institute of Medical Biology, Human Genetics and Embryology Laboratory, A(∗)STAR, Singapore 138648, Singapore.
2
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.

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.

PMID:
24316148
DOI:
10.1016/j.devcel.2013.11.002
[Indexed for MEDLINE]
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