RESUMEN
22q11-deletion (DiGeorge/velocardiofacial) syndrome (22q11DS) is modeled by mutation of murine transcription factor Tbx1. As part of efforts to identify transcriptional targets of Tbx1, we analyzed the transcriptome of the pharyngeal region of Df1/+;Tbx1+/- embryos at 9.5 days of embryonic development using two independent microarray platforms. In this model, embryos are null for Tbx1, with hemizygosity of genes in cis with Tbx1 on one chromosome providing a positive control for array sensitivity. Reduced mRNA levels of genes deleted from Df1 were detected on both platforms. Expression level filtering and statistical analysis identified several genes that were consistently differentially expressed between mutant and wild type embryos. Real-time quantitative PCR and in situ hybridization validated diminished expression of Pax9 and Gcm2, genes known to be required for normal thymus and parathyroid gland morphogenesis, whereas Pax1, Hoxa3, Eya1, and Foxn1, which are similarly required, were not down-regulated. Gbx2, a gene required for normal arch artery development, was down-regulated specifically in the pharyngeal endoderm and the posterior part of pharyngeal arch 1, and is a potential point of cross talk between the Tbx1 and Fgf8 controlled pathways. These experiments highlight which genes and pathways potentially affected by lack of Tbx1, and whose role may be explored further by testing for epistasis using mouse mutants.