Apelin signaling dependent endocardial protrusions promote cardiac trabeculation in zebrafish

Qi, Jialing; Rittershaus, Annegret; Priya, Rashmi; Mansingh, Shivani; Stainier, Didier Y. R.; Helker, Christian S. M.

doi:10.7554/elife.73231

Cited by 13 publications

(7 citation statements)

References 72 publications

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“…Time-lapse imaging from 55 to 72 hpf further showed a continuous junctional localization of the β-catenin chromobody in the endocardial cells ( ). This difference in junctional localization of the β-catenin chromobody in the endocardium versus endothelium of tnnt2a mutants might be explained by the strong inter-layer communication within the developing heart, especially the increasing tensile forces between the myocardium and endocardium ( Bornhorst et al, 2019 ; Priya et al, 2020 ; Qi et al, 2022 ) and/or the strong adhesive forces between endocardial cells during cardiac chamber expansion ( Mellman et al, 2012 ).…”

Section: Resultsmentioning

confidence: 99%

A β-catenin chromobody-based probe highlights endothelial maturation during vascular morphogenesis in vivo

Gauvrit,

Zhao,

Rothbauer

et al. 2024

Development

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Visualization of protein dynamics is a crucial step in understanding cellular processes. Chromobodies, fluorescently labelled single-domain antibodies, have emerged as versatile probes for live cell imaging of endogenous proteins. However, how these chromobodies behave in vivo and how accurately they monitor tissue changes remain poorly explored. Here, we generated an endothelial-specific β-catenin chromobody-derived probe and analyzed its expression pattern during cardiovascular development in zebrafish. Using high-resolution confocal imaging, we show that the chromobody signal correlates with the localization of β-catenin in the nucleus and at cell-cell junctions, and thereby can be used to assess endothelial maturation. Loss of Cadherin 5 strongly affects the localization of the chromobody at the cell membrane, confirming the cadherin-based adherens junction role of β-catenin. Furthermore, using a genetic model to block blood flow, we observed that cell junctions are compromised in most endothelial cells but not in the endocardium, highlighting the heterogeneous response of the endothelium to the lack of blood flow. Overall, our data further expand the use of chromobodies for in vivo applications and illustrate their potential to monitor tissue morphogenesis at high resolution.

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Section: Resultsmentioning

confidence: 99%

A β-catenin chromobody-based probe highlights endothelial maturation during vascular morphogenesis in vivo

Gauvrit,

Zhao,

Rothbauer

et al. 2024

Development

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“…However, how these factors affect cardiomyocyte behavior remains largely unknown and is currently under investigation. Recently it has been suggested that endocardial protrusions regulates communication between endocardium and myocardium by modulating Nrg/ErbB2 signaling 47, 48 . We favor a model in which Gpr126 either regulates the formation of endocardial protrusions or is transported to the myocardium through these protrusions.…”

Section: Discussionmentioning

confidence: 99%

Adgrg6/Gpr126 is required for myocardial Notch activity and N-cadherin localization to attain trabecular identity

Srivastava

Gunawan

Gentile

et al. 2022

Preprint

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How adhesion G protein-coupled receptors (aGPCRs) control development remains unclear. The aGPCR Adgrg6/Gpr126 has been associated with heart trabeculation. Defects in this process cause cardiomyopathies and embryonic lethality. Yet, how cardiomyocytes attain trabecular identity is poorly understood. Here, we show that Gpr126 regulates Notch activity and N-cadherin localization that are necessary for attaining trabecular identity in zebrafish. Maternal zygotic gpr126stl47 early truncation mutants exhibit hypotrabeculation whereby N-cadherin distributes randomly at apical/basal membranes of compact layer cardiomyocytes. In contrast, gpr126st49 mutants expressing a N-terminal fragment lacking the GPS motif (NTFΔGPS) exhibit a multilayered ventricular wall consisting of polarized cardiomyocytes with normal N-cadherin expression and increased Notch signaling. Notably, endocardially expressed C-terminal fragment (CTF) reinstates trabeculation in gpr126st49 mutants. Collectively, our data indicate domain-specific roles of Gpr126 during trabeculation whereby the NTF maintains cell-cell adhesion and is required for compact wall integrity, while the CTF is essential to provide trabecular identity.

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“…Parts of this chapter (4 Results) have been published as an article in the journal eLife (Qi et al eLife 2022;11: e73231. DOI: https://doi.org/10.7554/eLife.73231) (Qi et al, 2022).…”

Section: Resultsmentioning

confidence: 99%

“…This section (3.1.18 Zebrafish lines) is quoted from the article published in the journal eLife(Qi et al eLife 2022; 11: e73231. DOI: https://doi.org/10.7554/eLife.73231)(Qi et al, 2022).…”

mentioning

confidence: 99%

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

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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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Apelin signaling dependent endocardial protrusions promote cardiac trabeculation in zebrafish

Cited by 13 publications

References 72 publications

A β-catenin chromobody-based probe highlights endothelial maturation during vascular morphogenesis in vivo

A β-catenin chromobody-based probe highlights endothelial maturation during vascular morphogenesis in vivo

Adgrg6/Gpr126 is required for myocardial Notch activity and N-cadherin localization to attain trabecular identity

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

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