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Pitx2 confers left morphological, molecular, and functional identity to the sinus venosus myocardium
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SYSNO ASEP 0390178 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Pitx2 confers left morphological, molecular, and functional identity to the sinus venosus myocardium Author(s) Ammirabile, G. (IT)
Tessari, A. (IT)
Pignataro, V. (IT)
Szumska, D. (GB)
Sardo, F.S. (IT)
Beneš Jr., Jiří (FGU-C)
Balistreri, M. (IT)
Bhattacharya, S. (GB)
Sedmera, David (FGU-C) RID, ORCID, SAI
Campione, M. (IT)Source Title Cardiovascular Research - ISSN 0008-6363
Roč. 93, č. 2 (2012), s. 291-301Number of pages 11 s. Language eng - English Country NL - Netherlands Keywords Pitx2 ; sinus venosus myocardium ; optical mapping ; mouse cardiac development Subject RIV FA - Cardiovascular Diseases incl. Cardiotharic Surgery R&D Projects GA304/08/0615 GA ČR - Czech Science Foundation (CSF) CEZ AV0Z50110509 - FGU-C (2005-2011) UT WOS 000299415900013 DOI 10.1093/cvr/cvr314 Annotation The sinus venous myocardium, comprising the sinoatrial node (SAN) and sinus horns (SH), is a region subject to congenital malformations and cardiac arrhythmias. It differentiates from symmetric bilateral mesenchymal precursors, but morphological, molecular, and functional left/right differences are progressively established through development. The role of the laterality gene Pitx2 in this process is unknown. We aimed to elucidate the molecular events driving left/right patterning in the sinus venosus (SV) myocardium by using a myocardial Pitx2 knockout mouse. We generated a myocardial specific Pitx2 knockout model (cTP mice). cTP embryos present several features of Pitx2 null, including right atrial isomerism with bilateral SANs and symmetric atrial entrance of the systemic veins. By in situ hybridization and optical mapping analysis, we compared throughout development the molecular and functional properties of the SV myocardium in wt and mutant embryos. We observed that Pitx2 prevents the expansion of the left-SAN primordium at the onset of its differentiation into myocardium; Pitx2 promotes expansion of the left SH through development; Pitx2 dose-dependently represses the autorhythmic properties of the left SV myocardium at mid-gestation (E14.5); Pitx2 modulates late foetal gene expression at the left SH-derived superior caval vein. Pitx2 drives left/right patterning of the SV myocardium through multiple developmental steps. Overall, Pitx2 plays a crucial functional role by negatively modulating a nodal-type programme in the left SV myocardium Workplace Institute of Physiology Contact Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Year of Publishing 2013
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