Argonaute2 is essential for mammalian gastrulation and proper mesoderm formation

PLoS Genet. 2007 Dec 28;3(12):e227. doi: 10.1371/journal.pgen.0030227.


Mammalian Argonaute proteins (EIF2C1-4) play an essential role in RNA-induced silencing. Here, we show that the loss of eIF2C2 (Argonaute2 or Ago2) results in gastrulation arrest, ectopic expression of Brachyury (T), and mesoderm expansion. We identify a genetic interaction between Ago2 and T, as Ago2 haploinsufficiency partially rescues the classic T/+ short-tail phenotype. Finally, we demonstrate that the ectopic T expression and concomitant mesoderm expansion result from disrupted fibroblast growth factor signaling, likely due to aberrant expression of Eomesodermin. Together, these data indicate that a factor best known as a key component of the RNA-induced silencing complex is required for proper fibroblast growth factor signaling during gastrulation, suggesting a possible micro-RNA function in the formation of a mammalian germ layer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Argonaute Proteins
  • Base Sequence
  • Blotting, Western
  • DNA Primers
  • Eukaryotic Initiation Factor-2 / genetics
  • Eukaryotic Initiation Factor-2 / physiology*
  • Fetal Proteins / genetics
  • Fibroblast Growth Factors / metabolism
  • Gastrulation / physiology*
  • In Situ Hybridization
  • Mesoderm / growth & development*
  • Mice
  • RNA Interference
  • Signal Transduction
  • T-Box Domain Proteins / genetics


  • Ago2 protein, mouse
  • Argonaute Proteins
  • DNA Primers
  • Eukaryotic Initiation Factor-2
  • Fetal Proteins
  • T-Box Domain Proteins
  • Fibroblast Growth Factors
  • Brachyury protein