HIRA, a DiGeorge syndrome candidate gene, is required for cardiac outflow tract septation

DiGeorge syndrome (DGS) is a congenital disease characterized by defects in organs and tissues that depend on contributions by cell populations derive d from neural crest for proper development, A number of candidate genes tha t lie within the q11 region of chromosome 22 commonly deleted in DGS patien ts have been identified. Orthologues of the DGS candidate gene HIRA are exp ressed in the neural crest and in neural crest-derived tissues in both chic k and mouse embryos. By exposing a portion of the premigratory chick neural crest to phosphorothioate end-protected antisense oligonucleotides, ex ovo , followed by orthotopic backtransplantation to the untreated embryos, we h ave shown that the functional attenuation of cHIRA in the chick cardiac neu ral crest results in a significantly increased incidence of persistent trun cus arteriosus, a phenotypic change characteristic of DGS, but does not aff ect the repatterning aortic arch arteries, the ventricular function, or the alignment of the outflow tract.