Engrailed-1 as a target of the Wnt-1 signalling pathway in vertebrate midbrain development

Nature. 1996 Sep 26;383(6598):332-4. doi: 10.1038/383332a0.


A secreted signalling molecule encoded by the Wnt-1 gene is required for development of the central nervous system. In mouse embryos homozygous for a Wnt-1-null allele, the midbrain and anterior hindbrain fail to develop. This corresponds to the region where two transcription factors encoded by the mouse engrailed genes (En-1 and En-2) are normally expressed. Studies of the Drosophila orthologue of Wnt-1, wingless, indicate that Wingless signal is required to maintain engrailed expression in neighbouring cells of the developing epidermis. Here we report that expression of En-1 in the developing midbrain of Wnt-1-null embryos is sufficient to rescue early midbrain and anterior hindbrain development. This suggests that a key role of Wnt-1 signalling is to maintain En expression and that this aspect of the Wnt-1/engrailed interaction has been conserved from flies to mice.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Drosophila
  • Embryo, Mammalian / metabolism
  • Embryo, Nonmammalian
  • Enhancer Elements, Genetic
  • Female
  • Gene Expression Regulation, Developmental
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Male
  • Mesencephalon / anatomy & histology
  • Mesencephalon / embryology*
  • Mesencephalon / metabolism
  • Mice
  • Mice, Transgenic
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Rhombencephalon / embryology
  • Rhombencephalon / metabolism
  • Signal Transduction*
  • Wnt Proteins
  • Wnt1 Protein
  • Zebrafish Proteins*


  • En1 protein, mouse
  • Homeodomain Proteins
  • Proto-Oncogene Proteins
  • Wnt Proteins
  • Wnt1 Protein
  • Wnt1 protein, mouse
  • Zebrafish Proteins