Pitx2 confers left morphological, molecular, and functional identity to the sinus venosus myocardium.

Ammirabile, G; Tessari, A; Pignataro, V; Szumska, D; Sutera Sardo, F; Benes, J; Balistreri, M; Bhattacharya, S; Sedmera, D; Campione, M

Journal article

Pitx2 confers left morphological, molecular, and functional identity to the sinus venosus myocardium.

Abstract:: AIMS: 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. METHODS AND RESULTS: 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. CONCLUSION: 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.

Publication status:: Published

Actions

Email

Email this record

Send the bibliographic details of this record to your email address.

Your Email
Please enter the email address that the record information will be sent to.

-
Your message (optional)
Please add any additional information to be included within the email.
Cite

Cite this record

APA Style

Ammirabile, G., Tessari, A., Pignataro, V., Szumska, D., Sutera Sardo, F., Benes, J., Balistreri, M., Bhattacharya, S., Sedmera, D., & Campione, M. (2012). Pitx2 confers left morphological, molecular, and functional identity to the sinus venosus myocardium. Cardiovascular Research, 93(2), 291–301.

MLA Style

Ammirabile, G., et al. “Pitx2 Confers Left Morphological, Molecular, and Functional Identity to the Sinus Venosus Myocardium.” Cardiovascular Research, vol. 93, no. 2, 2012, pp. 291–301.

Chicago Style

Ammirabile, G, A Tessari, V Pignataro, D Szumska, F Sutera Sardo, J Benes, M Balistreri, S Bhattacharya, D Sedmera, and M Campione. 2012. “Pitx2 Confers Left Morphological, Molecular, and Functional Identity to the Sinus Venosus Myocardium.” Cardiovascular Research 93 (2): 291–301.
Share
Print