1. Developmental Biology
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The Apelin receptor enhances Nodal/TGFβ signaling to ensure proper cardiac development

  1. Ashish R Deshwar
  2. Serene C Chng
  3. Lena Ho
  4. Bruno Reversade
  5. Ian C Scott  Is a corresponding author
  1. The Hospital for Sick Children, Canada
  2. A*STAR, Singapore
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Cite this article as: eLife 2016;5:e13758 doi: 10.7554/eLife.13758

Abstract

The Apelin receptor (Aplnr) is essential for heart development, controlling the early migration of cardiac progenitors. Here we demonstrate that in zebrafish Aplnr modulates Nodal/TGFβ signaling, a key pathway essential for mesendoderm induction and migration. Loss of Aplnr function leads to a reduction in Nodal target gene expression whereas activation of Aplnr by a non-peptide agonist increases the expression of these same targets. Furthermore, loss of Aplnr results in a delay in the expression of the cardiogenic transcription factors mespaa/ab. Elevating Nodal levels in aplnra/b morphant and double mutant embryos is sufficient to rescue cardiac differentiation defects. We demonstrate that loss of Aplnr attenuates the activity of a point source of Nodal ligands Squint and Cyclops in a non-cell autonomous manner. Our results favour a model in which Aplnr is required to fine-tune Nodal output, acting as a specific rheostat for the Nodal/TGFβ pathway during the earliest stages of cardiogenesis.

Article and author information

Author details

  1. Ashish R Deshwar

    Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  2. Serene C Chng

    Institute of Medical Biology, A*STAR, Singapore, Singapore
    Competing interests
    The authors declare that no competing interests exist.
  3. Lena Ho

    Institute of Medical Biology, A*STAR, Singapore, Singapore
    Competing interests
    The authors declare that no competing interests exist.
  4. Bruno Reversade

    Institute of Medical Biology, A*STAR, Sinagapore, Singapore
    Competing interests
    The authors declare that no competing interests exist.
  5. Ian C Scott

    Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, Canada
    For correspondence
    ian.scott@sickkids.ca
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: Zebrafish were housed and handled as per Canadian Council on Animal Care and Hospital for Sick Children Laboratory Animal Services (LAS) guidelines under LAS protocol number 33584.

Reviewing Editor

  1. Elizabeth Robertson, University of Oxford, United Kingdom

Publication history

  1. Received: December 13, 2015
  2. Accepted: April 11, 2016
  3. Accepted Manuscript published: April 14, 2016 (version 1)
  4. Version of Record published: May 6, 2016 (version 2)

Copyright

© 2016, Deshwar et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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