22q11 Gene dosage establishes an adaptive range for sonic hedgehog and retinoic acid signaling during early development.

ABSTRACT: We asked whether key morphogenetic signaling pathways interact with 22q11 gene dosage to modulate the severity of cranial or cardiac anomalies in DiGeorge/22q1 deletion syndrome (22q11DS). Sonic hedgehog (Shh) and retinoic acid (RA) signaling is altered in the brain and heart-clinically significant 22q11DS phenotypic sites-in LgDel mouse embryos, an established 22q11DS model. LgDel embryos treated with cyclopamine, an Shh inhibitor, or carrying mutations in Gli3(Xtj), an Shh-signaling effector, have morphogenetic anomalies that are either not seen, or seen at significantly lower frequencies in control or single-mutant embryos. Similarly, RA exposure or genetic loss of RA function via heterozygous mutation of the RA synthetic enzyme Raldh2 induces novel cranial anomalies and enhances cardio

SUBMITTER: Maynard TM 

PROVIDER: S-EPMC3526161 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature