title: Origin, Specification, and Plasticity of the Great Vessels of the Heart.
abstract: The pharyngeal arch arteries (PAAs) are a series of paired embryonic blood vessels that give rise to several major arteries that connect directly to the heart. During development, the PAAs emerge from nkx2.5-expressing mesodermal cells and connect the dorsal head vasculature to the outflow tract of the heart. Despite their central role in establishing the circulatory system, the embryonic origins of the PAA progenitors are only coarsely defined, and the factors that specify them and their regenerative potential are unclear. Using fate mapping and mutant analysis, we find that PAA progenitors are derived from the tcf21 and nkx2.5 double-positive head mesoderm and require these two transcription factors for their specification and survival. Unexpectedly, cell ablation shows that the tcf21+; nkx2.5+ PAA progenitors are not required for PAA formation. We find that this compensation is due to the replacement of ablated tcf21+; nkx2.5+ PAA cells by endothelial cells from the dorsal head vasculature. Together, these studies assign the embryonic origin of the great vessel progenitors to the interface between the pharyngeal and cardiac mesoderm, identify the transcription factor code required for their specification, and reveal an unexpected plasticity in the formation of the great vessels.
authors.affiliation: Skirball Institute of Biomolecular Medicine, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA.
authors.forename: Danielle
authors.initials: D
authors.lastname: Nagelberg
authors.affiliation: Department of Cell Biology, Howard Hughes Medical Institute, Duke University Medical Center, 349 Nanaline Duke Building, Durham, NC 27710, USA.
authors.forename: Jinhu
authors.initials: J
authors.lastname: Wang
authors.affiliation: Skirball Institute of Biomolecular Medicine, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA.
authors.forename: Rina
authors.initials: R
authors.lastname: Su
authors.affiliation: Skirball Institute of Biomolecular Medicine, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA.
authors.forename: Jesús
authors.initials: J
authors.lastname: Torres-Vázquez
authors.affiliation: College of Physicians and Surgeons, Columbia University Medical Center, 630 West 168(th) Street, New York, NY 10023, USA.
authors.forename: Kimara L
authors.initials: KL
authors.lastname: Targoff
authors.affiliation: Department of Cell Biology, Howard Hughes Medical Institute, Duke University Medical Center, 349 Nanaline Duke Building, Durham, NC 27710, USA.
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Poss
authors.affiliation: Skirball Institute of Biomolecular Medicine, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA. Electronic address: holger.knaut@med.nyu.edu.
authors.forename: Holger
authors.initials: H
authors.lastname: Knaut
mesh_terms: D000818:Animals; D001934:Branchial Region / Q000196:embryology; D003331:Coronary Vessels / Q000196:embryology; D029941:Fish Proteins / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics
chemical_list: D029941:Fish Proteins; D014157:Transcription Factors