title: Fgf8 expression in the Tbx1 domain causes skeletal abnormalities and modifies the aortic arch but not the outflow tract phenotype of Tbx1 mutants.
abstract: Fgf8 and Tbx1 have been shown to interact in patterning the aortic arch, and both genes are required in formation and growth of the outflow tract of the heart. However, the nature of the interaction of the two genes is unclear. We have utilized a novel Tbx1(Fgf8) allele which drives Fgf8 expression in Tbx1-positive cells and an inducible Cre-LoxP recombination system to address the role of Fgf8 in Tbx1 positive cells in modulating cardiovascular development. Results support a requirement of Fgf8 in Tbx1 expressing cells to finely control patterning of the aortic arch and great arteries specifically during the pharyngeal arch artery remodeling process and indicate that the endoderm is the most likely site of this interaction. Furthermore, our data suggest that Fgf8 and Tbx1 play independent roles in regulating outflow tract development. This finding is clinically relevant since TBX1 is the candidate for DGS/VCFS, characterized clinically by variable expressivity and reduced penetrance of cardiovascular defects; Fgf8 gene variants may provide molecular clues to this variability.
authors.affiliation: Department of Pediatrics, Cardiology, Baylor College of Medicine, 1102 Bates St, RM FC450.03, Houston, TX 77030, USA. fvitelli@ibt.tamhsc.edu
authors.forename: Francesca
authors.initials: F
authors.lastname: Vitelli
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
authors.forename: Tuong
authors.initials: T
authors.lastname: Huynh
authors.forename: Angela
authors.initials: A
authors.lastname: Sobotka
authors.forename: Annalisa
authors.initials: A
authors.lastname: Mupo
authors.forename: Antonio
authors.initials: A
authors.lastname: Baldini
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000002:abnormalities*; D019521:Body Patterning; D001842:Bone and Bones / Q000002:abnormalities*; D001934:Branchial Region; D002319:Cardiovascular System / Q000254:growth & development; D004707:Endoderm; D051524:Fibroblast Growth Factor 8 / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D010641:Phenotype; D020825:T-Box Domain Proteins / Q000235:genetics*
chemical_list: C496457:Fgf8 protein, mouse; D020825:T-Box Domain Proteins; C491573:Tbx1 protein, mouse; D051524:Fibroblast Growth Factor 8