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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).
Pubmed ID: 21839921 RIS Download
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A portal to the Mouse Atlas of Gene Expression Project and Dissecting Gene Expression Networks in Mammalian Organogenesis Project. This Atlas will define the normal state for many tissues by determining, in a comprehensive and quantitative fashion, the number and identity of genes expressed throughout development. The resource will be comprehensive, quantitative, and publicly accessible, containing data on essentially all genes expressed throughout select stages of mouse development. Serial Analysis of Gene Expression (SAGE) is the gene expression methodology of choice for this work. Unlike expressed sequence tags (ESTs) and gene chip data, SAGE data are independent of prior gene discovery and are quantitative. Furthermore, SAGE data are digital, easily exchanged between laboratories for comparison and can be added to by scientists for years to come. Thus, this Atlas will include a data structure and data curation strategy that will facilitate the ongoing collection of gene expression data, even after the completion of this project. The Mouse Atlas project compromises 202 SAGE Libraries from 198 tissues. The list of libraries is available in a number of different groupings, including groups of libraries taken from specific tissue locations and libraries taken from specific developmental stages. Furthermore, this atlas will assemble gene expression profiles for a few focused experiments that will test hypotheses related to the techniques employed, tumor models and models of abnormal development. This will test the resource and provide quality control, validation and demonstrate applicability. Additionally, The Mammalian Organogenesis - Regulation by Gene Expression Networks (MORGEN) project will provide a complete, permanent, and accurate picture of mouse gene expression in the heart (atrioventricular canal and outflow tract), pancreas, and liver; new techniques to understand the interplay of proteins governing the expression of genes key to the development of these organ systems; and the identification of the master regulatory switches that control development of the tissues.
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