Notch and Bmp signaling pathways act coordinately during the formation of the proepicardium

Laura Andrés-Delgado; María Galardi-Castilla; Juliane Münch; Marina Peralta; Alexander Ernst; Juan Manuel González-Rosa; Federico Tessadori; Luis Santamaría; Jeroen Bakkers; Julien Vermot; José Luis de la Pompa; Nadia Mercader

doi:10.1002/dvdy.229

Notch and Bmp signaling pathways act coordinately during the formation of the proepicardium

Laura Andrés-Delgado, María Galardi-Castilla, Juliane Münch, Marina Peralta, Alexander Ernst, Juan Manuel González-Rosa, Federico Tessadori, Luis Santamaría, Jeroen Bakkers, Julien Vermot, José Luis de la Pompa, Nadia Mercader

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

7 Citations (Scopus)

Abstract

BACKGROUND: The epicardium is the outer mesothelial layer of the heart. It encloses the myocardium and plays key roles in heart development and regeneration. It derives from the proepicardium (PE), cell clusters that appear in the dorsal pericardium (DP) close to the atrioventricular canal and the venous pole of the heart, and are released into the pericardial cavity. PE cells are advected around the beating heart until they attach to the myocardium. Bmp and Notch signaling influence PE formation, but it is unclear how both signaling pathways interact during this process in the zebrafish.

RESULTS: Here, we show that the developing PE is influenced by Notch signaling derived from the endothelium. Overexpression of the intracellular receptor of notch in the endothelium enhances bmp expression, increases the number of pSmad1/5 positive cells in the DP and PE, and enhances PE formation. On the contrary, pharmacological inhibition of Notch1 impairs PE formation. bmp2b overexpression can rescue loss of PE formation in the presence of a Notch1 inhibitor, but Notch gain-of-function could not recover PE formation in the absence of Bmp signaling.

CONCLUSIONS: Endothelial Notch signaling activates bmp expression in the heart tube, which in turn induces PE cluster formation from the DP layer.

Original language	English
Journal	Developmental Dynamics
DOIs	https://doi.org/10.1002/dvdy.229
Publication status	E-pub ahead of print - 31 Jul 2020

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Andrés-Delgado, L., Galardi-Castilla, M., Münch, J., Peralta, M., Ernst, A., González-Rosa, J. M., Tessadori, F., Santamaría, L., Bakkers, J., Vermot, J., de la Pompa, J. L., & Mercader, N. (2020). Notch and Bmp signaling pathways act coordinately during the formation of the proepicardium. Developmental Dynamics. Advance online publication. https://doi.org/10.1002/dvdy.229

@article{6c2d2856f03544878f5fba8820457764,

title = "Notch and Bmp signaling pathways act coordinately during the formation of the proepicardium",

abstract = "BACKGROUND: The epicardium is the outer mesothelial layer of the heart. It encloses the myocardium and plays key roles in heart development and regeneration. It derives from the proepicardium (PE), cell clusters that appear in the dorsal pericardium (DP) close to the atrioventricular canal and the venous pole of the heart, and are released into the pericardial cavity. PE cells are advected around the beating heart until they attach to the myocardium. Bmp and Notch signaling influence PE formation, but it is unclear how both signaling pathways interact during this process in the zebrafish.RESULTS: Here, we show that the developing PE is influenced by Notch signaling derived from the endothelium. Overexpression of the intracellular receptor of notch in the endothelium enhances bmp expression, increases the number of pSmad1/5 positive cells in the DP and PE, and enhances PE formation. On the contrary, pharmacological inhibition of Notch1 impairs PE formation. bmp2b overexpression can rescue loss of PE formation in the presence of a Notch1 inhibitor, but Notch gain-of-function could not recover PE formation in the absence of Bmp signaling.CONCLUSIONS: Endothelial Notch signaling activates bmp expression in the heart tube, which in turn induces PE cluster formation from the DP layer.",

author = "Laura Andr{\'e}s-Delgado and Mar{\'i}a Galardi-Castilla and Juliane M{\"u}nch and Marina Peralta and Alexander Ernst and Gonz{\'a}lez-Rosa, {Juan Manuel} and Federico Tessadori and Luis Santamar{\'i}a and Jeroen Bakkers and Julien Vermot and {de la Pompa}, {Jos{\'e} Luis} and Nadia Mercader",

note = "{\textcopyright} 2020 The Authors. Developmental Dynamics published by Wiley Periodicals LLC on behalf of American Association of Anatomists.",

year = "2020",

month = jul,

day = "31",

doi = "10.1002/dvdy.229",

language = "English",

journal = "Developmental Dynamics",

issn = "1058-8388",

publisher = "Wiley-Liss Inc.",

}

TY - JOUR

T1 - Notch and Bmp signaling pathways act coordinately during the formation of the proepicardium

AU - Andrés-Delgado, Laura

AU - Galardi-Castilla, María

AU - Münch, Juliane

AU - Peralta, Marina

AU - Ernst, Alexander

AU - González-Rosa, Juan Manuel

AU - Tessadori, Federico

AU - Santamaría, Luis

AU - Bakkers, Jeroen

AU - Vermot, Julien

AU - de la Pompa, José Luis

AU - Mercader, Nadia

PY - 2020/7/31

Y1 - 2020/7/31

N2 - BACKGROUND: The epicardium is the outer mesothelial layer of the heart. It encloses the myocardium and plays key roles in heart development and regeneration. It derives from the proepicardium (PE), cell clusters that appear in the dorsal pericardium (DP) close to the atrioventricular canal and the venous pole of the heart, and are released into the pericardial cavity. PE cells are advected around the beating heart until they attach to the myocardium. Bmp and Notch signaling influence PE formation, but it is unclear how both signaling pathways interact during this process in the zebrafish.RESULTS: Here, we show that the developing PE is influenced by Notch signaling derived from the endothelium. Overexpression of the intracellular receptor of notch in the endothelium enhances bmp expression, increases the number of pSmad1/5 positive cells in the DP and PE, and enhances PE formation. On the contrary, pharmacological inhibition of Notch1 impairs PE formation. bmp2b overexpression can rescue loss of PE formation in the presence of a Notch1 inhibitor, but Notch gain-of-function could not recover PE formation in the absence of Bmp signaling.CONCLUSIONS: Endothelial Notch signaling activates bmp expression in the heart tube, which in turn induces PE cluster formation from the DP layer.

AB - BACKGROUND: The epicardium is the outer mesothelial layer of the heart. It encloses the myocardium and plays key roles in heart development and regeneration. It derives from the proepicardium (PE), cell clusters that appear in the dorsal pericardium (DP) close to the atrioventricular canal and the venous pole of the heart, and are released into the pericardial cavity. PE cells are advected around the beating heart until they attach to the myocardium. Bmp and Notch signaling influence PE formation, but it is unclear how both signaling pathways interact during this process in the zebrafish.RESULTS: Here, we show that the developing PE is influenced by Notch signaling derived from the endothelium. Overexpression of the intracellular receptor of notch in the endothelium enhances bmp expression, increases the number of pSmad1/5 positive cells in the DP and PE, and enhances PE formation. On the contrary, pharmacological inhibition of Notch1 impairs PE formation. bmp2b overexpression can rescue loss of PE formation in the presence of a Notch1 inhibitor, but Notch gain-of-function could not recover PE formation in the absence of Bmp signaling.CONCLUSIONS: Endothelial Notch signaling activates bmp expression in the heart tube, which in turn induces PE cluster formation from the DP layer.

U2 - 10.1002/dvdy.229

DO - 10.1002/dvdy.229

M3 - Article

C2 - 33103836

SN - 1058-8388

JO - Developmental Dynamics

JF - Developmental Dynamics

ER -

Notch and Bmp signaling pathways act coordinately during the formation of the proepicardium

Abstract

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