The role of Apelin signaling and endocardial protrusions during cardiac development in zebrafish

  • During cardiac development, cardiomyocytes (CMs) are delaminated from the compact muscle wall to increase the muscle mass of the heart. This process is also known as cardiac trabeculation. It has been shown that growth factors produced by endocardial cells (EdCs) are required for myocardial morphogenesis and growth. In particular, Neuregulin produced by EdCs promotes myocardial trabeculation. The deficiency of Neuregulin signaling leads to hypotrabeculation. Endocardial protrusions project from the endocardium to the myocardium are also essential for the trabeculae onset. Yet current studies only introduce the function of endocardial sprouts descriptively. This article first reports the mechanisms of endocardial sprouting during myocardial trabeculation. By living imaging, we first demonstrate that EdCs interact with CMs through membrane protrusions in zebrafish embryos. More interestingly, these protrusions stay in close contact with their target CMs in spite of the cardiac contraction. We utilize loss-of-function strategies to report the importance of myocardial apelin, which induces endocardial protrusion formation. Zebrafish lacking Apelin signaling exhibit defects in endocardial protrusion formation as well as excessive deposition of cardiac jelly and hypotrabeculation. Notably, we also present data that blocking protrusion formation in endocardial cells phenocopies the trabeculation defects in apelin mutants. Mechanistically, endocardial-derived Neuregulin requires Apelin signaling mediated endocardial protrusions, and Neuregulin dependent pERK expression is attenuated in the condition of reduced endocardial protrusion formation. Together, our data suggest that endocardial-myocardial communication through endocardial protrusions acts as an underlying principle allowing myocardial growth.

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Metadaten
Author:Jialing QiGND
URN:urn:nbn:de:hebis:30:3-817196
DOI:https://doi.org/10.21248/gups.81719
Place of publication:Frankfurt am Main
Referee:Didier Y. R. StainierORCiDGND, Virginie LecaudeyORCiDGND
Advisor:Didier Y. R. Stainier, Christian Helker
Document Type:Doctoral Thesis
Language:English
Date of Publication (online):2024/01/29
Year of first Publication:2023
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Granting Institution:Johann Wolfgang Goethe-Universität
Date of final exam:2023/12/20
Release Date:2024/01/29
Page Number:134
HeBIS-PPN:515109339
Institutes:Biowissenschaften / Biowissenschaften
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Sammlungen:Universitätspublikationen
Sammlung Biologie / Biologische Hochschulschriften (Goethe-Universität)
Licence (German):License LogoDeutsches Urheberrecht