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1: PLoS Genet. 2007 Dec 28;3(12):e227.Click here to read Click here to read Links

Argonaute2 is essential for mammalian gastrulation and proper mesoderm formation.

Alisch RS, Jin P, Epstein M, Caspary T, Warren ST.

Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, United States of America.

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.

PMID: 18166081 [PubMed - indexed for MEDLINE]

PMCID: PMC2323323