Positional cloning of a global regulator of anterior-posterior patterning in mice.
Anterior-posterior (A-P) patterning is of fundamental importance throughout vertebrate embryonic development. Murine members of the trithorax (trx) and Polycomb group (Pc-G) of genes regulate A-P patterning of segmented axial structures, demonstrating conserved upstream regulation of homeotic pathways between Drosophila and mouse. Here we report the positional cloning of a classical mouse mutation, eed (for embryonic ectoderm development), which is the highly conserved homologue of the Drosophila Pc-G gene esc (for extra sex combs), a long-term repressor of homeotic genes. Mutants homozygous for a null allele of eed display disrupted A-P patterning of the primitive streak during gastrulation. Mutant embryos lack a node, notochord and somites, and there is no neural induction. In contrast to absence of anterior structures, extra-embryonic mesoderm is abundant. Mice carrying a hypomorphic eed mutation exhibit posterior transformations along the axial skeleton. These results indicate that eed is required globally for A-P patterning throughout embryogenesis.
Shumacher
A
A
Department of Genetics, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Faust
C
C
Magnuson
T
T
D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D018899:CpG Islands; D004330:Drosophila / Q000235:genetics; D029721:Drosophila Proteins; D005314:Embryonic and Fetal Development / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D011495:Histone-Lysine N-Methyltransferase; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009024:Morphogenesis / Q000235:genetics; D009154:Mutation; D063150:Polycomb Repressive Complex 1; D063151:Polycomb Repressive Complex 2; D011506:Proteins / Q000235:genetics; D017386:Sequence Homology, Amino Acid
D029721:Drosophila Proteins; C066770:Pc protein, Drosophila; D011506:Proteins; D011495:Histone-Lysine N-Methyltransferase; D063151:Polycomb Repressive Complex 2; C543389:esc protein, Drosophila; D063150:Polycomb Repressive Complex 1