2026-07-21T09:56:01Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/133022024-09-27T09:39:46Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Andres-Delgado, Laura author Galardi-Castilla, Maria author Munch, Juliane author Peralta, Marina author Ernst, Alexander author Gonzalez-Rosa, Juan Manuel author Tessadori, Federico author Santamaria, Luis author Bakkers, Jeroen author Vermot, Julien author de la Pompa, Jose Luis author Mercader, Nadia author 2020-12 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. 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. Endothelial Notch signaling activates bmp expression in the heart tube, which in turn induces PE cluster formation from the DP layer. Dev Dyn. 2020; 249(12):1455-1469 10.1002/dvdy.229 1058-8388 Developmental dynamics: an official publication of the American Association of Anatomists 33103836 http://hdl.handle.net/20.500.12105/13302 Notch and Bmp signaling pathways act coordinately during the formation of the proepicardium.