Dp1 is required for extra-embryonic development.
Release of E2F1/DP1 heterodimers from repression mediated by the retinoblastoma tumor suppressor (pRB) triggers cell cycle entry into S phase, suggesting that E2F1 and DP1 proteins must act in unison, either to facilitate or to suppress cell-cycle progression. In stark contrast to the milder phenotypes that result from inactivation of E2Fs, we report that loss of Dp1 leads to death in utero because of the failure of extra-embryonic development. Loss of Dp1 compromises the trophectoderm-derived tissues - specifically, the expansion of the ectoplacental cone and chorion, and endoreduplication in trophoblast giant cells. Inactivation of p53 is unable to rescue the Dp1-deficient embryonic lethality. Thus, DP1 is absolutely required for extra-embryonic development and consequently embryonic survival, consistent with E2F/DP1 normally acting to promote growth in vivo.
Kohn
Matthew J
MJ
Department of Biological Sciences, Columbia University, New York, NY 10027 USA.
Bronson
Roderick T
RT
Harlow
Ed
E
Dyson
Nicholas J
NJ
Yamasaki
Lili
L
D000818:Animals; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D005313:Fetal Death / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D005804:Genes, Lethal; D051379:Mice; D018345:Mice, Knockout; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014327:Trophoblasts / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493754:E2f1 protein, mouse; C493736:Tfdp1 protein, mouse; C490579:Tfdp2 protein, mouse; D050680:Transcription Factor DP1; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53