Hoxa1 and Hoxb1 are required for pharyngeal arch artery development

Abstract

Hox transcription factors play critical roles during early vertebrate development. Previous studies have revealed an overlapping function of Hoxa1 and Hoxb1 during specification of the rhombomeres from which neural crest cells emerge. A recent study on Hoxa1 mutant mice documented its function during cardiovascular development, however, the role of Hoxb1 is still unclear. Here we show using single and compound Hoxa1;Hoxb1 mutant embryos that reduction of Hoxa1 gene dosage in Hoxb1-null genetic background is sufficient to result in abnormal pharyngeal aortic arch (PAA) development and subsequently in great artery defects. Endothelial cells in the 4th PAAs of compound mutant differentiate normally whereas vascular smooth muscle cells of the vessels are absent in the defective PAAs. The importance of Hoxa1 and Hoxb1, and their interaction during specification of cardiac NCCs is demonstrated. Together, our data reveal a critical role for anterior Hox genes during PAA development, providing new mechanistic insights into the etiology of congenital heart defects.

Keywords: Congenital heart defects; Great arteries; Hox; Mouse; Neural crest cells; Pharyngeal arch arteries.