Argonaute2 is essential for mammalian gastrulation and proper mesoderm formation.
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.
Alisch
Reid S
RS
Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, United States of America.
Jin
Peng
P
Epstein
Michael
M
Caspary
Tamara
T
Warren
Stephen T
ST
D000818:Animals; D060565:Argonaute Proteins; D001483:Base Sequence; D015153:Blotting, Western; D017931:DNA Primers; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics / Q000502:physiology*; D005326:Fetal Proteins / Q000235:genetics; D005346:Fibroblast Growth Factors / Q000378:metabolism; D054262:Gastrulation / Q000502:physiology*; D017403:In Situ Hybridization; D008648:Mesoderm / Q000254:growth & development*; D051379:Mice; D034622:RNA Interference; D015398:Signal Transduction; D020825:T-Box Domain Proteins / Q000235:genetics; D000098908:Brachyury Protein
D060565:Argonaute Proteins; D017931:DNA Primers; D015852:Eukaryotic Initiation Factor-2; D005326:Fetal Proteins; D005346:Fibroblast Growth Factors; D020825:T-Box Domain Proteins; D000098908:Brachyury Protein; C526735:Ago2 protein, mouse