Positional cloning of a global regulator of anterior-posterior patterning in mice

Nature. 1996 Sep 19;383(6597):250-3. doi: 10.1038/383250a0.

Abstract

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.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cloning, Molecular
  • CpG Islands
  • Drosophila / genetics
  • Drosophila Proteins*
  • Embryonic and Fetal Development / genetics*
  • Gene Expression Regulation, Developmental*
  • Histone-Lysine N-Methyltransferase
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Morphogenesis / genetics
  • Mutation
  • Polycomb Repressive Complex 1
  • Polycomb Repressive Complex 2
  • Proteins / genetics
  • Sequence Homology, Amino Acid

Substances

  • Drosophila Proteins
  • Pc protein, Drosophila
  • Proteins
  • Histone-Lysine N-Methyltransferase
  • Polycomb Repressive Complex 2
  • esc protein, Drosophila
  • Polycomb Repressive Complex 1