E2F4 cooperates with pRB in the development of extra-embryonic tissues.

ABSTRACT: The retinoblastoma gene, RB-1, was the first identified tumor suppressor. Rb(-/-) mice die in mid-gestation with defects in proliferation, differentiation and apoptosis. The activating E2F transcription factors, E2F1-3, contribute to these embryonic defects, indicating that they are key downstream targets of the retinoblastoma protein, pRB. E2F4 is the major pRB-associated E2F in vivo, yet its role in Rb(-/-) embryos is unknown. Here we establish that E2f4 deficiency reduced the lifespan of Rb(-/-) embryos by exacerbating the Rb mutant placental defect. We further show that this reflects the accumulation of trophectoderm-like cells in both Rb and Rb;E2f4 mutant placentas. Thus, Rb and E2f4 play cooperative roles in placental development. We used a conditional mouse model to allow Rb(-/-);E

SUBMITTER: Lee EY 

PROVIDER: S-EPMC2832217 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature