title: Tbx1 expression in pharyngeal epithelia is necessary for pharyngeal arch artery development.
abstract: During embryonic life, the initially paired pharyngeal arch arteries (PAAs) follow a precisely orchestrated program of persistence and regression that leads to the formation of the mature aortic arch and great vessels. When this program fails, specific cardiovascular defects arise that may be life threatening or mild, according to the identity of the affected artery. Fourth PAA-derived cardiovascular defects occur commonly in DiGeorge syndrome and velocardiofacial syndrome (22q11DS), and in Tbx1(+/-) mice that model the 22q11DS cardiovascular phenotype. Tbx1 is expressed in pharyngeal mesoderm, endoderm and ectoderm, and, in addition, we show that it is expressed in precursors of the endothelial cells that line the PAAs, thus expanding the number of tissues in which Tbx1 is potentially required for fourth PAA development. In this study, we have used cell fate mapping and tissue-specific gene deletion, driven by six different Cre lines, to explore Tbx1 gene-dosage requirements in the embryonic pharynx for fourth PAA development. Through this approach, we have resolved the spatial requirements for Tbx1 in this process, and we show pharyngeal epithelia to be a critical tissue. We also thereby demonstrate conclusively that the role of Tbx1 in fourth PAA development is cell non-autonomous.
authors.affiliation: Department of Pediatrics (Cardiology), Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
authors.forename: Fabiana
authors.initials: F
authors.lastname: Cerrato
authors.forename: Huansheng
authors.initials: H
authors.lastname: Xu
authors.forename: Francesca
authors.initials: F
authors.lastname: Vitelli
authors.forename: Masae
authors.initials: M
authors.lastname: Morishima
authors.forename: Joshua
authors.initials: J
authors.lastname: Vincentz
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Furuta
authors.forename: Lijiang
authors.initials: L
authors.lastname: Ma
authors.forename: James F
authors.initials: JF
authors.lastname: Martin
authors.forename: Antonio
authors.initials: A
authors.lastname: Baldini
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Lindsay
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic; D001158:Arteries / Q000254:growth & development*; D001934:Branchial Region / Q000098:blood supply*; D004622:Embryo, Mammalian; D004848:Epithelium / Q000737:chemistry / Q000502:physiology*; D017353:Gene Deletion; D018628:Gene Dosage; D051379:Mice; D008815:Mice, Inbred Strains; D010614:Pharynx / Q000196:embryology; D020825:T-Box Domain Proteins / Q000235:genetics* / Q000502:physiology*
chemical_list: D020825:T-Box Domain Proteins; C491573:Tbx1 protein, mouse