ELABELA: A HORMONE ESSENTIAL FOR HEART DEVELOPMENT SIGNALS VIA THE APELIN RECEPTOR

Abstract

PEPTIDE HORMONES ARE AN IMPORTANT GROUP OF SECRETED SIGNALLING MOLECULES THAT REGULATE MANY PHYSIOLOGICAL FUNCTIONS. WE WOULD LIKE TO DETAIL THE DISCOVERY AND CHARACTERIZATION OF THE GENE ELABELA (ELA), A CONSERVED GENE ENCODING A HORMONE OF 32 AMINO-ACIDS. PRESENT IN HESCS, ELA IS EXPRESSED AT THE ONSET OF ZEBRAFISH ZYGOTIC TRANSCRIPTION AND IS UBIQUITOUS IN THE ECTODERMAL CELLS OF THE EMBRYO. ELA MUTANTS HAVE IMPAIRED MESENDODERM DIFFERENTIATION POTENTIAL AND DEVELOP WITH RUDIMENTARY OR ABSENT HEARTS. SURPRISINGLY PHENOCOPY THE LOSS OF THE APLNR, WHICH WE SHOW SERVES AS ITS COGNATE CELL-SURFACE GPCR. WE FOUND THAT APLNR SIGNALLING PROMOTES NODAL/TGF? SIGNALLING DURING GASTRULATION, A KEY PATHWAY FOR MESENDODERM INDUCTION AND MIGRATION. UNEXPECTEDLY, IN THE CONTEXT OF NODAL MODULATION, ELA APPEARS TO HAVE OPPOSING EFFECTS TO THAT OF APLNR. WE PROPOSE A NOVEL MECHANISM WHEREBY APLNR/ELA FUNCTION AS A RHEOSTAT THAT FINE-TUNES NODAL SIGNALLING LEVELS TO ALLOW PROPER MESENDODERM SPECIFICA