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Hippo signaling determines the number of venous pole cells that originate from the anterior lateral plate mesoderm in zebrafish

  1. Hajime Fukui
  2. Takahiro Miyazaki
  3. Renee Wei-Yan Chow
  4. Hiroyuki Ishikawa
  5. Hiroyuki Nakajima
  6. Julien Vermot
  7. Naoki Mochizuki  Is a corresponding author
  1. National Cerebral and Cardiovascular Center Research Institute, Japan
  2. Institut de Génétique et de Biologie Moléculaire et Cellulaire, France
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Cite this article as: eLife 2018;7:e29106 doi: 10.7554/eLife.29106

Abstract

The differentiation of the lateral plate mesoderm cells into heart field cells constitutes a critical step in the development of cardiac tissue and the genesis of functional cardiomyocytes. Hippo signaling controls cardiomyocyte proliferation, but the role of Hippo signaling during early cardiogenesis remains unclear. Here, we show that Hippo signaling regulates atrial cell number by specifying the developmental potential of cells within the anterior lateral plate mesoderm (ALPM), which are incorporated into the venous pole of the heart tube and ultimately into the atrium of the heart. We demonstrate that Hippo signaling acts through large tumor suppressor kinase 1/2 to modulate BMP signaling and the expression of hand2, a key transcription factor that is involved in the differentiation of atrial cardiomyocytes. Collectively, these results demonstrate that Hippo signaling defines venous pole cardiomyocyte number by modulating both the number and the identity of the ALPM cells that will populate the atrium of the heart.

Article and author information

Author details

  1. Hajime Fukui

    Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, Suita, Japan
    Competing interests
    The authors declare that no competing interests exist.
  2. Takahiro Miyazaki

    Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, Suita, Japan
    Competing interests
    The authors declare that no competing interests exist.
  3. Renee Wei-Yan Chow

    Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Hiroyuki Ishikawa

    Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, Suita, Japan
    Competing interests
    The authors declare that no competing interests exist.
  5. Hiroyuki Nakajima

    Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, Suita, Japan
    Competing interests
    The authors declare that no competing interests exist.
  6. Julien Vermot

    Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8924-732X
  7. Naoki Mochizuki

    Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, Suita, Japan
    For correspondence
    mochizuki@ncvc.go.jp
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3938-9602

Funding

Japan Society for the Promotion of Science (16H02618)

  • Naoki Mochizuki

Ministry of Education, Culture, Sports, Science, and Technology (15H01221)

  • Hajime Fukui

Japan Agency for Medical Research and Development (13414779)

  • Naoki Mochizuki

Takeda Medical Research Foundation

  • Naoki Mochizuki

Takeda Medical Research Foundation

  • Hajime Fukui

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Animal experimentation: The experiments using zebrafish were approved by the institutional animal committee of National Cerebral and Cardiovascular Center (Permit number:17003) and performed according to the guidelines of the Institute.

Reviewing Editor

  1. Deborah Yelon, University of California, San Diego, United States

Publication history

  1. Received: May 30, 2017
  2. Accepted: May 26, 2018
  3. Accepted Manuscript published: May 29, 2018 (version 1)
  4. Version of Record published: June 11, 2018 (version 2)

Copyright

© 2018, Fukui 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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