We herein reported thatHedgehog signaling is one of the causative factors for omphalocele formation,as demonstrated by utilizing a series of combinatorial mutants for Hh signalinggenes and conditional gain-of-function mutants of the Hh signaling pathway.The analyses of Shh, Gli3 and Alx4 compoundmutant embryos revealed that the introduction of additional Alx4Lstmutations into the Gli3Xt/Xt background resultedin the corresponding omphalocele and pubic diastasis. This evidence concerns the gene SHH and omphalocele.