Logo image
Back
Chapter 4.3 - Pitx2 in Cardiac Left–Right Asymmetry and Human Disease
Book chapter

Chapter 4.3 - Pitx2 in Cardiac Left–Right Asymmetry and Human Disease

James F. Martin, Brad A. Amendt and Nigel A. Brown
Heart Development and Regeneration, pp.307-322
Elsevier Inc
2010
DOI: 10.1016/B978-0-12-381332-9.00015-3

View Online

Abstract

This chapter discusses the importance of Pitx2 in cardiac left-right asymmetry and human disease. Left–right asymmetry defects were recognized to be a causative factor in congenital heart disease, but usually in the context of other syndromes. Recent experiments in human genetics mapping loci responsible for familial atrial fibrillation have suggested a connection between left–right asymmetry and atrial fibrillation, a common cardiac anomaly involving abnormal cardiac rhythm afflicting a large percentage of the adult population. Thus, left–right asymmetry has important consequences for the development of a normal body plan and a correctly functioning adult heart. Early models held that a linear signaling cascade asymmetrically patterned all developing organs. However, study of Pitx2 regulation has revealed that multiple pathways, such as Wnt and Bmp signaling, likely feed into left–right asymmetry morphogenesis. One challenge in the future will be to determine the mechanisms of signaling pathway convergence and overlap. Moreover, since Pitx2 is a major effector of the Nodal-mediated pathway and is critical for normal cardiac development, it will be important to gain more comprehensive insight into Pitx2 target genes. The finding that the second heart field is asymmetrically patterned by Pitx2 provides the opportunity to dissect the genetic pathways regulating second heart field development. It will be important to understand how Pitx2 regulates transcription in the heart by interacting with histone-modifying and chromatin-remodeling complexes.

Details

Metrics

22 Record Views
Logo image