Platelet-derived growth factor (PDGF) signaling directs cardiomyocyte movement toward the midline during heart tube assembly
- University of California, San Diego, United States
- Victor Chang Cardiac Research Institute, Australia
Abstract
Communication between neighboring tissues plays a central role in guiding organ morphogenesis. During heart tube assembly, interactions with the adjacent endoderm control the medial movement of cardiomyocytes, a process referred to as cardiac fusion. However, the molecular underpinnings of this endodermal-myocardial relationship remain unclear. Here, we show an essential role for platelet-derived growth factor receptor alpha (Pdgfra) in directing cardiac fusion. Mutation of pdgfra disrupts heart tube assembly in both zebrafish and mouse. Timelapse analysis of individual cardiomyocyte trajectories reveals misdirected cells in zebrafish pdgfra mutants, suggesting that PDGF signaling steers cardiomyocytes toward the midline during cardiac fusion. Intriguingly, the ligand pdgfaa is expressed in the endoderm medial to the pdgfra-expressing myocardial precursors. Ectopic expression of pdgfaa interferes with cardiac fusion, consistent with an instructive role for PDGF signaling. Together, these data uncover a novel mechanism through which endodermal-myocardial communication can guide the cell movements that initiate cardiac morphogenesis.
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Author details
Funding
National Heart, Lung, and Blood Institute (R01HL081911 and R01HL133166)
- Deborah Yelon
March of Dimes Foundation (1-FY11-493)
- Deborah Yelon
National Health and Medical Research Council (NHMRC 1074386; 573732; 5737707; 573705)
- Owen WJ Prall
- Richard P Harvey
Australian Research Council (Stem Cells Australia SR110001002)
- Richard P Harvey
American Heart Association (12POST11660038)
- Joshua Bloomekatz
Australian Heart Foundation (CR 08S 3958)
- Owen WJ Prall
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All zebrafish work followed protocols approved by the UCSD IACUC (protocol S09125). All mouse experiments were overseen by the Garvan Institute of Medical Research/St. Vincent's Hospital Animal Ethics Committee (projects AEC13/01 and AEC13/02).
Copyright
© 2017, Bloomekatz 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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Platelet-derived growth factor (PDGF) signaling directs cardiomyocyte movement toward the midline during heart tube assembly
eLife 6:e21172.
https://doi.org/10.7554/eLife.21172
