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.
Danielian
P S
PS
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
McMahon
A P
AP
D000818:Animals; D004330:Drosophila; D004622:Embryo, Mammalian / Q000378:metabolism; D004625:Embryo, Nonmammalian; D004742:Enhancer Elements, Genetic; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008636:Mesencephalon / Q000033:anatomy & histology / Q000196:embryology* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012249:Rhombencephalon / Q000196:embryology / Q000378:metabolism; D015398:Signal Transduction; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins
C080330:En1 protein, mouse; D018398:Homeodomain Proteins; D011518:Proto-Oncogene Proteins; D051153:Wnt Proteins; D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse; D029961:Zebrafish Proteins