This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kohn, M. J. Articles by Yamasaki, L. Search for Related Content PubMed PubMed Citation Articles by Kohn, M. J. Articles by Yamasaki, L.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, August 2004, p. 7197-7205, Vol. 24, No. 16
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.16.7197-7205.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Dp1 Is Largely Dispensable for Embryonic Development

Matthew J. Kohn, Sandra W. Leung, Vittoria Criniti, Monica Agromayor, and Lili Yamasaki^*

Department of Biological Sciences, Columbia University, New York, New York 10027

Received 26 January 2004/ Returned for modification 23 March 2004/ Accepted 26 May 2004

E2F/DP complexes activate or repress the transcription of E2F target genes, depending on the association of a pRB family member, thereby regulating cell cycle progression. Whereas the E2F family consists of seven members, the DP family contains only two (Dp1 and Dp2), Dp1 being the more highly expressed member. In contrast to the inactivation of individual E2F family members, we have recently demonstrated that loss of Dp1 results in embryonic lethality by embryonic day 12.5 (E12.5) due to the failure of extraembryonic lineages to develop and replicate DNA properly. To bypass this placental requirement and search for roles of Dp1 in the embryo proper, we generated Dp1-deficient embryonic stem (ES) cells that carry the ROSA26-LacZ marker and injected them into wild-type blastocysts to construct Dp1-deficient chimeras. Surprisingly, we recovered mid- to late gestational embryos (E12.5 to E17.5), in which the Dp1-deficient ES cells contributed strongly to most chimeric tissues as judged by X-Gal (5-bromo-4-chloro-3-indolyl-ß-D-galactopyranoside) staining and Western blotting. Importantly, the abundance of DP2 protein does not increase and the expression of an array of cell cycle genes is virtually unchanged in Dp1-deficient ES cells or chimeric E15.5 tissues with the absence of Dp1. Thus, Dp1 is largely dispensable for embryonic development, despite the absolute extraembryonic requirement for Dp1, which is highly reminiscent of the restricted roles for Rb and cyclins E1/E2 in vivo.

Present address: National Institutes of Health/NICHD, Bethesda, MD 20892.

This article has been cited by other articles:

• Qiao, H., Di Stefano, L., Tian, C., Li, Y.-Y., Yin, Y.-H., Qian, X.-P., Pang, X.-W., Li, Y., McNutt, M. A., Helin, K., Zhang, Y., Chen, W.-F. (2007). Human TFDP3, a Novel DP Protein, Inhibits DNA Binding and Transactivation by E2F. J. Biol. Chem. 282: 454-466 [Abstract] [Full Text]  
• Park, J.-M., Kohn, M. J., Bruinsma, M. W., Vech, C., Intine, R. V., Fuhrmann, S., Grinberg, A., Mukherjee, I., Love, P. E., Ko, M. S., DePamphilis, M. L., Maraia, R. J. (2006). The Multifunctional RNA-Binding Protein La Is Required for Mouse Development and for the Establishment of Embryonic Stem Cells. Mol. Cell. Biol. 26: 1445-1451 [Abstract] [Full Text]  
• Maehara, K., Yamakoshi, K., Ohtani, N., Kubo, Y., Takahashi, A., Arase, S., Jones, N., Hara, E. (2005). Reduction of total E2F/DP activity induces senescence-like cell cycle arrest in cancer cells lacking functional pRB and p53. J. Cell Biol. 168: 553-560 [Abstract] [Full Text]