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Author Notes:

Corresponding author: Stephen T Warren, Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, United States of America. Email: swarren@genetics.emory.edu.

RSA, PJ, and TC conceived and designed the experiments. RSA performed the experiments. RSA, ME, TC, and STW analyzed the data. RSA and STW contributed reagents/materials/analysis tools. RSA, TC, and STW wrote the paper.

We are grateful to Brigid Hogan and Deidre Mattiske for introducing us to early embryo methodology. We appreciate the gifts of Brachyury antibody and the immunohistochemistry protocol from Yina Li and Chin Chiang.

We thank Robert Baul, Anne Dodd, Tamika Malone, and Julie Mowrey for technical assistance, as well as Karen Artzt, Maria Garcia-Garcia, Gail Martin, and Olga Peñagarikano for their comments.

The authors have declared that no competing interests exist.

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Research Funding:

This work was supported, in part, by National Institutes of Health grants HD20521 and HD24064 (STW) and the FRAXA Research Foundation (RSA).

Argonaute2 Is Essential for Mammalian Gastrulation and Proper Mesoderm Formation

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Journal Title:

PLoS Genetics

Volume:

Volume 3, Number 12

Publisher:

, Pages e227-e227

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

© 2007 Alisch et al.

This is an Open Access article distributed under the terms of the Creative Commons Attribution 3.0 Unported License ( http://creativecommons.org/licenses/by/3.0/), which permits distribution, public display, and publicly performance, distribution of derivative works, making multiple copies, provided the original work is properly cited. This license requires copyright and license notices be kept intact, credit be given to copyright holder and/or author.

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