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(Circulation Research. 2008;102:749.)
© 2008 American Heart Association, Inc.

Editorials

Pitx2

A Challenging Teenager

Robert E. Poelmann, Monique R.M. Jongbloed, Adriana C. Gittenberger-de Groot

From the Department of Anatomy & Embryology, Leiden University Medical Center, Leiden, The Netherlands.

Correspondence to Prof Dr Adriana C. Gittenberger-de Groot, Department of Anatomy & Embryology, Leiden University Medical Center, S-1-P, PO Box 9600, 2300 RC Leiden, The Netherlands. E-mail acgitten@lumc.nl

See related article, pages 813–822

Key Words: Pitx2 • left–right asymmetry • cardiac morphogenesis • second heart field

An extract of the first 250 words of the full text is provided, because this article has no abstract.

In this issue of Circulation Research, Tessari et al¹ investigate the role of an interesting gene, Pitx2, which acts in breaking symmetry in early development and has subsequent roles in differentiation of the inflow and outflow segment of the heart. Already almost 10 years ago, the transcription factor Pitx2 was demonstrated by several groups to be expressed asymmetrical in the early embryo and present in the left-sided plate mesoderm only.^2–4 It is a target gene of Nodal and is kept from leaking to the right side of the midline barrier by Lefty1. The Nodal–Lefty–Pitx2 module is conserved in vertebrates, although the earliest phases in breaking symmetry show similarities, as well as differences, among zebrafish, birds, and mammals.⁵ The Pitx2 gene is also described in chordates and echinoderms, proving its evolutionary ancestry. The Pitx2c variant seems to be cardiac-specific and triggers a cascade involving Nkx, Gata, and Hand. These genes are important for the early phase of cardiac development, starting with the bilateral cardiogenic fields and their fusion to form the cardiac tube. The next stage, rightward cardiac looping, is reported to be either dependent⁶ or independent of Pitx2.⁷ Recently, the involvement of the second heart field, contributing to both the arterial pole (anterior and secondary heart field) and the venous pole (posterior heart field), has gained importance. Therefore, many other genes governed or cofactored by Pitx2 can be added to the list of cardiac determinants, or at least as determinants of specific parts of the heart. These include the . . . [Full Text of this Article]

Related Article:

Myocardial Pitx2 Differentially Regulates the Left Atrial Identity and Ventricular Asymmetric Remodeling Programs

Alessandra Tessari, Mara Pietrobon, Antonella Notte, Giuseppe Cifelli, Philip J. Gage, Michael D. Schneider, Giuseppe Lembo, and Marina Campione
Circ. Res. 2008 102: 813-822. [Abstract] [Full Text] [PDF]