Nodal antagonists in the anterior visceral endoderm prevent the formation of multiple primitive streaks

Dev Cell. 2002 Nov;3(5):745-56. doi: 10.1016/s1534-5807(02)00321-0.


The anterior visceral endoderm plays a pivotal role in establishing anterior-posterior polarity of the mouse embryo, but the molecular nature of the signals required remains to be determined. Here, we demonstrate that Cerberus-like(-/-);Lefty1(-/-) compound mutants can develop a primitive streak ectopically in the embryo. This defect is not rescued in chimeras containing wild-type embryonic, and Cerberus-like(-/-);Lefty1(-/-) extraembryonic, cells but is rescued in Cerberus-like(-/-); Lefty1(-/-) embryos after removal of one copy of the Nodal gene. Our findings provide support for a model whereby Cerberus-like and Lefty1 in the anterior visceral endoderm restrict primitive streak formation to the posterior end of mouse embryos by antagonizing Nodal signaling. Both antagonists are also required for proper patterning of the primitive streak.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Patterning / physiology*
  • Cytokines
  • Embryonic and Fetal Development
  • Endoderm / physiology*
  • Gastrula / physiology*
  • Left-Right Determination Factors
  • Mice
  • Mutagenesis
  • Nodal Protein
  • Phenotype
  • Proteins / genetics
  • Proteins / physiology*
  • Signal Transduction*
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism*
  • Transforming Growth Factor beta / physiology*


  • Cer1 protein, mouse
  • Cytokines
  • Left-Right Determination Factors
  • Nodal Protein
  • Nodal protein, mouse
  • Proteins
  • Transforming Growth Factor beta