title: 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.
authors.affiliation: Aix Marseille Univ, INSERM, GMGF, Marseille, France.
authors.forename: Marine
authors.initials: M
authors.lastname: Roux
authors.affiliation: Aix Marseille Univ, INSERM, GMGF, Marseille, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Laforest
authors.affiliation: Aix Marseille Univ, INSERM, GMGF, Marseille, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Eudes
authors.affiliation: Aix Marseille Univ, INSERM, GMGF, Marseille, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bertrand
authors.affiliation: Aix Marseille Univ, INSERM, GMGF, Marseille, France.
authors.forename: Sonia
authors.initials: S
authors.lastname: Stefanovic
authors.affiliation: Aix Marseille Univ, INSERM, GMGF, Marseille, France. Electronic address: stephane.zaffran@univ-amu.fr.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Zaffran
mesh_terms: D000818:Animals; D001934:Branchial Region / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D002454:Cell Differentiation; D004622:Embryo, Mammalian; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D018628:Gene Dosage; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009024:Morphogenesis / Q000235:genetics; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000235:genetics*; D015398:Signal Transduction; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics*; D000099261:Homeobox A1 Protein
chemical_list: D018398:Homeodomain Proteins; D014157:Transcription Factors; D000099261:Homeobox A1 Protein; C101121:HOXB1 homeodomain protein
keywords: Congenital heart defects; Great arteries; Hox; Mouse; Neural crest cells; Pharyngeal arch arteries