The myocardium utilizes a platelet-derived growth factor receptor alpha (Pdgfra) - phosphoinositide 3-kinase (PI3K) signaling cascade to steer towards the midline during zebrafish heart tube formation
- University of Mississippi, United States
Abstract
Coordinated cell movement is a fundamental process in organ formation. During heart development, bilateral myocardial precursors collectively move towards the midline (cardiac fusion) to form the primitive heart tube. Extrinsic influences such as the adjacent anterior endoderm are known to be required for cardiac fusion. We previously showed however, that the platelet-derived growth factor receptor alpha (Pdgfra) is also required for cardiac fusion (Bloomekatz et al. 2017). Nevertheless, an intrinsic mechanism that regulates myocardial movement has not been elucidated. Here, we show that the phosphoinositide 3-kinase (PI3K) intracellular signaling pathway has an essential intrinsic role in the myocardium directing movement towards the midline. In vivo imaging further reveals midline-oriented dynamic myocardial membrane protrusions that become unpolarized in PI3K-inhibited zebrafish embryos where myocardial movements are misdirected and slower. Moreover, we find that PI3K activity is dependent on and interacts with Pdgfra to regulate myocardial movement. Together our findings reveal an intrinsic myocardial steering mechanism that responds to extrinsic cues during the initiation of cardiac development.
Data availability
All data are included in the manuscript and supporting files; Source Data files have been provided for all figures.
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Author details
Funding
American Heart Association (18CDA34080195)
- Joshua Bloomekatz
Eunice Kennedy Shriver National Institute of Child Health and Human Development (R15HD108782)
- Joshua Bloomekatz
National Institute of General Medical Sciences (P20GM103460)
- Joshua Bloomekatz
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 animals were handled according to protocols approved by the University of Mississippi institutional animal care and use committee (IACUC) (protocol #21-007), in accordance with the recommendations of the National Institutes of Health (NIH).
Copyright
© 2023, Shrestha 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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The myocardium utilizes a platelet-derived growth factor receptor alpha (Pdgfra) - phosphoinositide 3-kinase (PI3K) signaling cascade to steer towards the midline during zebrafish heart tube formation
eLife 12:e85930.
https://doi.org/10.7554/eLife.85930
