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Molecular and Cellular Biology, August 2005, p. 7193-7202, Vol. 25, No. 16
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.16.7193-7202.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Rybp/DEDAF Is Required for Early Postimplantation and for Central Nervous System Development

Melinda K. Pirity,1 Joseph Locker,2 and Nicole Schreiber-Agus1*

Department of Molecular Genetics,1 Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 104612

Received 4 February 2005/ Returned for modification 26 April 2005/ Accepted 1 June 2005

The Rybp/DEDAF protein has been implicated in both transcriptional regulation and apoptotic signaling, but its precise molecular function is unclear. To determine the physiological role of Rybp, we analyzed its expression during mouse development and generated mice carrying a targeted deletion of Rybp using homologous recombination in embryonic stem cells. Rybp was found to be broadly expressed during embryogenesis and was particularly abundant in extraembryonic tissues, including trophoblast giant cells. Consistent with this result, rybp homozygous null embryos exhibited lethality at the early postimplantation stage. At this time, Rybp was essential for survival of the embryo, for the establishment of functional extraembryonic structures, and for the execution of full decidualization. Through the use of a chimeric approach, the embryonic lethal phenotype was circumvented and a role for Rybp in central nervous system development was uncovered. Specifically, the presence of Rybp-deficient cells resulted in marked forebrain overgrowth and in localized regions of disrupted neural tube closure. Functions for Rybp in the brain also were supported by the finding of exencephaly in about 15% of rybp heterozygous mutant embryos, and by Rybp's distinct neural expression pattern. Together, these findings support critical roles for Rybp at multiple stages of mouse embryogenesis.

* Corresponding author. Mailing address: 1300 Morris Park Avenue, Ullmann 809, Bronx, NY 10461. Phone: (718) 430-3216. Fax: (718) 430-8778. E-mail: agus{at}aecom.yu.edu.

Molecular and Cellular Biology, August 2005, p. 7193-7202, Vol. 25, No. 16
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.16.7193-7202.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Gonzalez, I., Aparicio, R., Busturia, A. (2008). Functional Characterization of the dRYBP Gene in Drosophila. Genetics 179: 1373-1388 [Abstract] [Full Text]  
  • Stanton, S. E., McReynolds, L. J., Evans, T., Schreiber-Agus, N. (2006). Yaf2 Inhibits Caspase 8-mediated Apoptosis and Regulates Cell Survival during Zebrafish Embryogenesis. J. Biol. Chem. 281: 28782-28793 [Abstract] [Full Text]  


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