title: Fgf15 is required for proper morphogenesis of the mouse cardiac outflow tract.
abstract: Evidence in animal models indicates that signaling networks functioning in the developing pharyngeal arches regulate stereotyped processes critical for proper development of the aortic arch and cardiac outflow tract. Here, we describe the phenotype of mice lacking fibroblast growth factor 15 (Fgf15), which encodes a secreted signaling molecule expressed within the developing pharyngeal arches. Homozygous Fgf15 mutants present heart defects consistent with malalignment of the aorta and pulmonary trunk. These defects correlate with early morphological defects of the outflow tract due to aberrant behavior of the cardiac neural crest. We demonstrate that Fgf15 expression within the pharyngeal arches is unaltered by a loss of Tbx1, a key regulator of pharyngeal arch development implicated in DiGeorge syndrome. In addition, Fgf15 and Tbx1 do not interact genetically, suggesting that Fgf15 operates through a pathway independent of Tbx1. These studies reveal a novel role of Fgf15 during development of the cardiac outflow tract.
authors.affiliation: Program in Genes and Development, Graduate School of Biomedical Sciences, University of Texas-Houston, Health Sciences Center and M. D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Joshua W
authors.initials: JW
authors.lastname: Vincentz
authors.forename: John R
authors.initials: JR
authors.lastname: McWhirter
authors.forename: Cornelis
authors.initials: C
authors.lastname: Murre
authors.forename: Antonio
authors.initials: A
authors.lastname: Baldini
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Furuta
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000002:abnormalities / Q000196:embryology*; D001934:Branchial Region / Q000196:embryology; D016923:Cell Death; D049109:Cell Proliferation; D005346:Fibroblast Growth Factors / Q000502:physiology*; D005838:Genotype; D006330:Heart Defects, Congenital / Q000235:genetics*; D017403:In Situ Hybridization; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D015398:Signal Transduction; D020825:T-Box Domain Proteins / Q000235:genetics / Q000502:physiology
chemical_list: D020825:T-Box Domain Proteins; C491573:Tbx1 protein, mouse; C108526:fibroblast growth factor 15, mouse; D005346:Fibroblast Growth Factors