Antisense targeting of engrailed-1 causes abnormal axis formation in mouse embryos

Antisense oligonucleotide targeting of engrailed-1 (En-1) in early somite mouse embryos resulted in reduced En protein levels and produced abnormalities of the brain, face, and heart and shortening of the embryonic axis (caudal dysgenesis). Defects of the brain and limbs were consistent with abnormalities observed in null mutant mice described by other investigators. Abnormalities of the face and heart may be related to alterations in neural crest cells. Caudal dysgenesis suggested a role for En-1 in axis formation and this hypothesis was supported by results showing that En-1 protein and mRNA are present in the primitive streak. Thus, in addition to participating in the signaling pathway for brain and limb development, En-1 appears to play a role in patterning the embryonic axis.