Notch initiates the endothelial-to-mesenchymal transition in the atrioventricular canal through autocrine activation of soluble guanylyl cyclase - PubMed (original) (raw)

. 2011 Aug 16;21(2):288-300.

doi: 10.1016/j.devcel.2011.06.022.

YangXin Fu, Victoria C Garside, Kyle Niessen, Linda Chang, Megan Fuller, Audi Setiadi, Justin Smrz, Alastair Kyle, Andrew Minchinton, Marco Marra, Pamela A Hoodless, Aly Karsan

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Notch initiates the endothelial-to-mesenchymal transition in the atrioventricular canal through autocrine activation of soluble guanylyl cyclase

Alex C Y Chang et al. Dev Cell. 2011.

Free article

Abstract

The heart is the most common site of congenital defects, and valvuloseptal defects are the most common of the cardiac anomalies seen in the newborn. The process of endothelial-to-mesenchymal transition (EndMT) in the cardiac cushions is a required step during early valve development, and Notch signaling is required for this process. Here we show that Notch activation induces the transcription of both subunits of the soluble guanylyl cyclase (sGC) heterodimer, GUCY1A3 and GUCY1B3, which form the nitric oxide receptor. In parallel, Notch also promotes nitric oxide (NO) production by inducing Activin A, thereby activating a PI3-kinase/Akt pathway to phosphorylate eNOS. We thus show that the activation of sGC by NO through a Notch-dependent autocrine loop is necessary to drive early EndMT in the developing atrioventricular canal (AVC).

Copyright © 2011 Elsevier Inc. All rights reserved.

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