2026-07-21T20:41:05Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/55282024-09-27T08:06:01Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
VanDusen, Nathan J.
author
Casanovas, Jose
author
Vincentz, Joshua W.
author
Firulli, Beth A.
author
Osterwalder, Marco
author
Lopez-Rios, Javier
author
Zeller, Rolf
author
Zhou, Bin
author
Grego-Bessa, Joaquim
author
de la Pompa, Jose Luis
author
Shou, Weinian
author
Firulli, Anthony B.
funder
Riley Childrens Foundation
funder
National Institutes of Health (Estados Unidos)
funder
American Heart Association
2017-12-01T07:37:28Z
2017-12-01T07:37:28Z
2014
Cell Rep. 2014; 9(6):2071-83
10.1016/j.celrep.2014.11.021
2211-1247
Cell Reports
25497097
http://hdl.handle.net/20.500.12105/5528
The basic-helix-loop-helix (bHLH) transcription factor Hand2 plays critical roles during cardiac morphogenesis via expression and function within myocardial, neural crest, and epicardial cell populations. Here, we show that Hand2 plays two essential Notch-dependent roles within the endocardium. Endocardial ablation of Hand2 results in failure to develop a patent tricuspid valve, intraventricular septum defects, and hypotrabeculated ventricles, which collectively resemble the human congenital defect tricuspid atresia. We show endocardial Hand2 to be an integral downstream component of a Notch endocardium-to-myocardium signaling pathway and a direct transcriptional regulator of Neuregulin1. Additionally, Hand2 participates in endocardium-to-endocardium-based cell signaling, with Hand2 mutant hearts displaying an increased density of coronary lumens. Molecular analyses further reveal dysregulation of several crucial components of Vegf signaling, including VegfA, VegfR2, Nrp1, and VegfR3. Thus, Hand2 functions as a crucial downstream transcriptional effector of endocardial Notch signaling during both cardiogenesis and coronary vasculogenesis.
eng
CORONARY-ARTERIES
ENDOTHELIAL-CELLS
TRICUSPID-ATRESIA
CARDIAC GROWTH
HEART-DISEASE
DNA-BINDING
LIMB BUD
IN-VIVO
GENE
ANGIOGENESIS
Hand2 Is an Essential Regulator for Two Notch-Dependent Functions within the Embryonic Endocardium
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Hand2IsAnEssentialRegulator_2014_SM1.pdf
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Hand2IsAnEssentialRegulator_2014.pdf.txt
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