title: Partial rescue of the Tbx1 mutant heart phenotype by Fgf8: genetic evidence of impaired tissue response to Fgf8.
abstract: Tbx1 is the candidate gene of DiGeorge syndrome and is required in humans and mice for the development of the cardiac outflow tract (OFT) and aortic arch arteries. Loss of function mutants present with reduced cell proliferation and premature differentiation of cardiac progenitor cells of the second heart field (SHF). Tbx1 regulates Fgf8 expression hence the hypothesis that the proliferation impairment may contribute to the heart phenotype of mutants. Here we show that forced Fgf8 expression modifies and partially rescues the OFT septation defects of Tbx1 mutants but only if there is some residual expression of Tbx1. This genetic experiment suggests that Tbx1, directly or indirectly, affects tissue response to Fgf8. Indeed, Tbx1(-/-) mouse embryonic fibroblasts were unable to respond to Fgf8 added to the culture media and showed defective response of Erk1/2 and Rsk1. Our data suggest a coordinated pathway modulating Fgf8 ligand expression and tissue response to it in the SHF.
authors.affiliation: Institute of Biosciences and Technologies, Texas A&M University, Houston, TX, USA.
authors.forename: Francesca
authors.initials: F
authors.lastname: Vitelli
authors.forename: Gabriella
authors.initials: G
authors.lastname: Lania
authors.forename: Tuong
authors.initials: T
authors.lastname: Huynh
authors.forename: Antonio
authors.initials: A
authors.lastname: Baldini
mesh_terms: D000818:Animals; D015153:Blotting, Western; D051524:Fibroblast Growth Factor 8 / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009154:Mutation / Q000235:genetics*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D010641:Phenotype; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism
chemical_list: C496457:Fgf8 protein, mouse; D020825:T-Box Domain Proteins; C491573:Tbx1 protein, mouse; D051524:Fibroblast Growth Factor 8; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C512964:Rps6ka1 protein, mouse
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