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

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.