Dissection of Tbx1 and Fgf interactions in mouse models of 22q11DS suggests functional redundancy

Vimla S. Aggarwal, Jun Liao, Alexei Bondarev, Thomas Schimmang, Mark Lewandoski, Joseph Locker, Alan Shanske, Marina Campione, Bernice E. Morrow

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


The 22q11 deletion syndrome (22q11DS) is characterized by abnormal development of the pharyngeal apparatus. Mouse genetic studies have identified Tbx1 as a key gene in the etiology of the syndrome, in part, via interaction with the fibroblast growth factor (Fgf) genes. Three murine Fgfs, Fgf3, Fgf8 and Fgf10 are coexpressed in different combinations with Tbx1. They are all strongly downregulated in Tbx1-/- embryos, implicating epistatic interactions. Supporting this, Tbx1 and Fgf8 have been shown to genetically interact in the development of the fourth pharyngeal arch artery (PAA) and Fgf10 was identified to be a direct downstream target of Tbx1. To dissect the epistatic relationships of these genes during embryonic development and the molecular pathogenesis of the Tbx1 mutant phenotype, we generated Fgf10+/- Tbx1+/- and Fgf3-/-; Tbx1+/- mice. Despite strong hypotheses that Fgf10 is the key gene downstream of Tbx1 in the development of the anterior heart field, we do not find evidence for genetic interaction between Tbx1 and Fgf10. Also, the Fgf3-/-; Tbx1+/- mutant mice do not show an additive phenotype. Furthermore, more severe defects do not occur in Fgf8+/-; Tbx1+/- mutants by crossing in the Fgf3 null allele. There is a possible additive effect only in PAA remodeling in the Fgf10+/-; Tbx1+/-; Fgf8+/- embryos. Our findings underscore the importance of potential functional redundancy with additional Fgfs in the development of the pharyngeal apparatus and cardiovascular system via Tbx1. This redundancy should be considered when looking at individual FGF genes as modifiers of 22q11DS.

Original languageEnglish (US)
Pages (from-to)3219-3228
Number of pages10
JournalHuman molecular genetics
Issue number21
StatePublished - Nov 1 2006

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)


Dive into the research topics of 'Dissection of Tbx1 and Fgf interactions in mouse models of 22q11DS suggests functional redundancy'. Together they form a unique fingerprint.

Cite this