A molecular programme for the specification of germ cell fate in mice

Nature. 2002 Jul 18;418(6895):293-300. doi: 10.1038/nature00927.

Abstract

Germ cell fate in mice is induced in proximal epiblast cells by the extra-embryonic ectoderm, and is not acquired through the inheritance of any preformed germ plasm. To determine precisely how germ cells are specified, we performed a genetic screen between single nascent germ cells and their somatic neighbours that share common ancestry. Here we show that fragilis, an interferon-inducible transmembrane protein, marks the onset of germ cell competence, and we propose that through homotypic association, it demarcates germ cells from somatic neighbours. Using single-cell gene expression profiles, we also show that only those cells with the highest expression of fragilis subsequently express stella, a gene that we detected exclusively in lineage-restricted germ cells. The stella positive nascent germ cells exhibit repression of homeobox genes, which may explain their escape from a somatic cell fate and the retention of pluripotency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Proteins / deficiency
  • Bone Morphogenetic Proteins / genetics
  • Bone Morphogenetic Proteins / metabolism
  • Cell Differentiation*
  • Cell Lineage*
  • Chromosomal Proteins, Non-Histone
  • Down-Regulation
  • Ectoderm / cytology
  • Ectoderm / physiology
  • Embryonic Induction
  • Female
  • Gene Deletion
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental*
  • Genes, Homeobox / genetics
  • Germ Cells / cytology*
  • Germ Cells / metabolism*
  • Immunohistochemistry
  • In Situ Hybridization
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Knockout
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism

Substances

  • Bmp4 protein, mouse
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Proteins
  • Chromosomal Proteins, Non-Histone
  • Dppa3 protein, mouse
  • Membrane Proteins
  • RNA, Messenger
  • Repressor Proteins
  • fragilis protein, mouse