A genetic link between Tbx1 and fibroblast growth factor signaling

Francesca Vitelli, Ilaria Taddei, Masae Morishima, Erik N. Meyers, Elizabeth A. Lindsay, Antonio Baldini

Research output: Contribution to journalArticlepeer-review


Tbx1 haploinsufficiency causes aortic arch abnormalities in mice because of early growth and remodeling defects of the fourth pharyngeal arch arteries. The function of Tbx1 in the development of these arteries is probably cell non-autonomous, as the gene is not expressed in structural components of the artery but in the surrounding pharyngeal endoderm. We hypothesized that Tbx1 may trigger signals from the pharyngeal endoderm directed to the underlying mesenchyme. We show that the expression patterns of Fgf8 and Fgf10, which partially overlap with Tbx1 expression pattern, are altered in Tbx1-/- mutants. In particular, Fgf8 expression is abolished in the pharyngeal endoderm. To understand the significance of this finding for the pathogenesis of the mutant Tbx1 phenotype, we crossed Tbx1 and Fgf8 mutants. Double heterozygous Tbx1+/-;Fgf8+/- mutants present with a significantly higher penetrance of aortic arch artery defects than do Tbx1/-;Fgf8+/+ mutants, while Tbx1+/+;Fg8+/- animals are normal. We found that Fgf8 mutation increases the severity of the primary defect caused by Tbx1 haploinsufficiency, i.e. early hypoplasia of the fourth pharyngeal arch arteries, consistent with the time and location of the shared expression domain of the two genes. Hence, Tbx1 and Fgf8 interact genetically in the development of the aortic arch. Our data provide the first evidence of a genetic link between Tbx1 and FGF signaling, and the first example of a modifier of the Tbx1 haploinsufficiency phenotype. We speculate that the FGF8 locus might affect the penetrance of cardiovascular defects in individuals with chromosome 22q11 deletions involving TBX1.

Original languageEnglish
Pages (from-to)4605-4611
Number of pages7
Issue number19
Publication statusPublished - Oct 2002


  • Pharyngeal arch arteries
  • Pharyngeal endoderm
  • Phenotypic modifiers

ASJC Scopus subject areas

  • Anatomy
  • Cell Biology


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