Visualization of outflow tract development in the absence of Tbx1 using an FgF10 enhancer trap transgene.

Tbx1, the major gene underlying del22q11.2 or DiGeorge syndrome in humans, is required for normal development and septation of the cardiac outflow tract. The fibroblast growth factor 10 gene (Fgf10) and an Fgf10 enhancer trap transgene are expressed in outflow tract myocardial progenitor cells of the anterior heart field. To visualize outflow tract development in the absence of Tbx1, we have analyzed the expression profile of the Fgf10 enhancer trap transgene during outflow tract development in Tbx1(-/-) embryos. Transgene expression confirms hypoplasia of the distal outflow tract in the absence of Tbx1, and altered expression in pharyngeal mesoderm reveals loss of specific bilateral subpopulations of outflow tract progenitor cells and disruption of the posterior boundary of the anterior heart field. Our results support the conclusion that Tbx1 controls deployment of Fgf10-expressing progenitor cells during heart tube extension. Furthermore, although normal Fgf10 levels are dependent on Tbx1, loss of Fgf10 alleles does not significantly modify the cardiac phenotype of Tbx1 heterozygous or homozygous mutant embryos.