Transcription factor AP-2gamma is essential in the extra-embryonic lineages for early postimplantation development.
The members of the AP-2 family of transcription factors play important roles during mammalian development and morphogenesis. AP-2gamma (Tcfap2c - Mouse Genome Informatics) is a retinoic acid-responsive gene implicated in placental development and the progression of human breast cancer. We show that AP-2gamma is present in all cells of preimplantation embryos and becomes restricted to the extra-embryonic lineages at the time of implantation. To study further the biological function of AP-2gamma, we have generated Tcfap2c-deficient mice by gene disruption. The majority of Tcfap2c(-/-) mice failed to survive beyond 8.5 days post coitum (d.p.c.). At 7.5 d.p.c., Tcfap2c(-/-) mutants were typically arrested or retarded in their embryonic development in comparison to controls. Morphological and molecular analyses of mutants revealed that gastrulation could be initiated and that anterior-posterior patterning of the epiblast remained intact. However, the Tcfap2c mutants failed to establish a normal maternal-embryonic interface, and the extra-embryonic tissues were malformed. Moreover, the trophoblast-specific expression of eomesodermin and Cdx2, two genes implicated in FGF-responsive trophoblast stem cell maintenance, was significantly reduced. Chimera studies demonstrated that AP-2gamma plays no major autonomous role in the development of the embryo proper. By contrast, the presence of AP-2gamma in the extra-embryonic membranes is required for normal development of this compartment and also for survival of the mouse embryo.
Auman
Heidi J
HJ
Department of Molecular, Cellular and Developmental Biology, Yale University, 266 Whitney Avenue, New Haven, CT 06511, USA.
Nottoli
Timothy
T
Lakiza
Olga
O
Winger
Quinton
Q
Donaldson
Stephanie
S
Williams
Trevor
T
D000818:Animals; D001755:Blastocyst / Q000502:physiology; D001943:Breast Neoplasms / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D010064:Embryo Implantation; D005314:Embryonic and Fetal Development / Q000235:genetics*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D005838:Genotype; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis; D010920:Placenta / Q000502:physiology; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D015183:Restriction Mapping; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*
D004268:DNA-Binding Proteins; C493679:TFAP2C protein, human; C583890:Tfap2c protein, mouse; D050656:Transcription Factor AP-2; D014157:Transcription Factors