Congenital heart defects (CHD) are the leading cause of death in the first year of life. Over the past 20 years, much effort has been focused on unraveling the genetic bases of CHD. In particular, studies in human genetics coupled with those of model organisms have provided valuable insights into the gene regulatory networks underlying CHD pathogenesis. Hox genes encode transcription factors that are required for the patterning of the anterior-posterior axis in the embryo. In this review, we focus on the emerging role of anteriorly expressed Hox genes (Hoxa1, Hoxb1, and Hoxa3) in cardiac development, specifically their contribution to patterning of cardiac progenitor cells and formation of the great arteries. Recent evidence regarding the cooperative regulation of heart development by Hox proteins with members of the TALE-class of homeodomain proteins such as Pbx and Meis transcription factors is also discussed. These findings are highly relevant to human pathologies as they pinpoint new genes that increase susceptibility to cardiac anomalies and provide novel mechanistic insights into CHD.
Keywords: Hox; cardiogenesis; heart development; pharyngeal aortic arches; second heart field; transcription factors.