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PMID: 18166081 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Argonaute2 is essential for mammalian gastrulation and proper mesoderm formation.

PLoS genetics ·Vol. 3 ·No. 12 ·2007-12-28 ·Pages e227

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

Abstract

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.

MeSH Terms
Animals Argonaute Proteins Base Sequence Blotting, Western DNA Primers Eukaryotic Initiation Factor-2/genetics,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
Chemicals
Ago2 protein, mouse Argonaute Proteins DNA Primers Eukaryotic Initiation Factor-2 Fetal Proteins T-Box Domain Proteins Fibroblast Growth Factors Brachyury protein
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Alisch Reid S
Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, United States of America.
Jin Peng
Epstein Michael
Caspary Tamara
Warren Stephen T
Conflict of Interest

Competing interests. The authors have declared that no competing interests exist.

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Article Info
Journal
PLoS genetics
Abbr.
PLoS Genet
ISSN
1553-7404
DOI
10.1371/journal.pgen.0030227
Published
2007-12-28
Pages
e227
Language
English
Region
United States
NLM ID
101239074
PMCID
PMC2323323
Subset
IM
Grants
NICHD NIH HHS · R37 HD020521 · United States
NICHD NIH HHS · HD20521 · United States
NICHD NIH HHS · P30 HD024064 · United States
NICHD NIH HHS · R01 HD020521 · United States
NIMH NIH HHS · R01 MH076090 · United States
NICHD NIH HHS · HD24064 · United States
External Links
PubMed source DOI: 10.1371/journal.pgen.0030227 PMC Full Text View journal details
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