Hippo signaling determines the number of venous pole cells that originate from the anterior lateral plate mesoderm in zebrafish
- National Cerebral and Cardiovascular Center Research Institute, Japan
- Institut de Génétique et de Biologie Moléculaire et Cellulaire, France
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.
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All data generated or analyzed during this study are included in the manuscript.
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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.
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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Hippo signaling determines the number of venous pole cells that originate from the anterior lateral plate mesoderm in zebrafish
eLife 7:e29106.
https://doi.org/10.7554/eLife.29106
