argonaute2 is essential for mammalian gastrulation and proper mesoderm formationargonaute2对哺乳动物的原肠胚形成和适当的中胚层的形成至关重要.pdf

Argonaute2 Is Essential for Mammalian Gastrulation and Proper Mesoderm Formation 1 1 1 1 1,2,3* Reid S. Alisch , Peng Jin , Michael Epstein , Tamara Caspary , Stephen T. Warren 1 Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, United States of America, 2 Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia, United States of America, 3 Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, United States of America Mammalian Argonaute proteins (EIF2C14) 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/þ 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. Citation: Alisch RS, Jin P, Epstein M, Caspary T, Warren ST (2007) Argonaute2 is essential for mammalian gastrulation and proper mesoderm formation. PLoS Genet 3(12): e227. doi:10.1371/journal.pgen.0030227 Introduction generate a mouse line that transmits an interrupted Ago2 allele without an obvious het