Apelin signaling dependent endocardial protrusions promote cardiac trabeculation in zebrafish
- Max Planck Institute for Heart and Lung Research, Germany
- Philipps-University Marburg, Germany
Abstract
During cardiac development, endocardial cells (EdCs) produce growth factors to promote myocardial morphogenesis and growth. In particular, EdCs produce Neuregulin which is required for ventricular cardiomyocytes (CMs) to seed the multicellular ridges known as trabeculae. Defects in Neuregulin signaling, or in endocardial sprouting towards CMs, cause hypotrabeculation. However, the mechanisms underlying endocardial sprouting remain largely unknown. Here, we first show by live imaging in zebrafish embryos that EdCs interact with CMs via dynamic membrane protrusions. After touching CMs, these protrusions remain in close contact with their target despite the vigorous cardiac contractions. Loss of the CM-derived peptide Apelin, or of the Apelin receptor, which is expressed in EdCs, leads to reduced endocardial sprouting and hypotrabeculation. Mechanistically, Neuregulin signaling requires endocardial protrusions to induce extracellular signal-regulated kinase (Erk) activity in CMs and trigger their delamination. Altogether, these data show that Apelin signaling dependent endocardial protrusions modulate CM behavior during trabeculation.
Data availability
Figure 2 - Source Data 1, Figure 4 - Source Data 1, Figure 5 - Source Data 1, Figure 6 - Source Data 1, and Supplementary File 1 contain the numerical data used to generate the figures.
Article and author information
Author details
Didier YR Stainier
Christian SM Helker
Funding
Max-Planck-Gesellschaft
- Didier YR Stainier
Deutsche Forschungsgemeinschaft (SFB834)
- Didier YR Stainier
- Christian SM Helker
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 husbandry was performed under standard conditions in accordance with institutional (MPG) and national (German) ethical and animal welfare regulations. All experiments conducted on animals conform to the guidelines from Directive 2010/63/EU of the European Parliament on the protection of animals used for scientific purposes and were approved by the Animal Protection Committee (Tierschutzkommission) of the Regierungspräsidium Darmstadt (Proposal numbers: B2/1017, B2/1041, B2/1138, B2/1218).
Copyright
© 2022, Qi 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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Apelin signaling dependent endocardial protrusions promote cardiac trabeculation in zebrafish
eLife 11:e73231.
https://doi.org/10.7554/eLife.73231
