Argonaute2 Is Essential for Mammalian Gastrulation and Proper Mesoderm Formation

• Type of Material: Article
• Authors: Richelle Reid, Emory University; Peng Jin, Emory University; Michael Epstein, Emory University; Tamara Caspary, Emory University; Stephen Warren, Emory University
• Language: English
• Date: 2007-12
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2007 Alisch et al.
• License: Creative Commons Attribution 3.0 Unported
• Final Published Version (URL): http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.0030227
• Title of Journal or Parent Work: PLoS Genetics
• ISSN: 1553-7390
• Volume: 3
• Issue: 12
• Start Page: e227
• End Page: e227
• Grant/Funding Information: This work was supported, in part, by National Institutes of Health grants HD20521 and HD24064 (STW) and the FRAXA Research Foundation (RSA).
• Research Categories: Biology, Genetics; Health Sciences, Obstetrics and Gynecology; Chemistry, Biochemistry

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.