PubMed Health⌕ Search

Biomedical subjects

Quinton Winger

Publications and source records attributed to Quinton Winger.

2 recordsLinked to original sources

Analysis of transcription factor AP-2 expression and function during mouse preimplantation development.

The activating protein 2 (AP-2) transcription factor family is required for multiple aspects of mouse postimplantation development, but much less is known about the expression and possible function of these genes during the preimplantation period. In the present study, we have examined the expression of all five members of the mouse AP-2 gene family in the unfertilized oocyte and from zygote formation to the blastocyst stage of development. Four AP-2 genes are differentially expressed during the preimplantation period,Tcfap2a, Tcfap2b, Tcfap2c, and Tcfap2e. Furthermore, with the exception of Tcfap2a, these genes are also expressed in unfertilized oocytes, indicating that they may be important for oogenesis, maternal-effect functions, or both. Given these findings, we have initiated studies to assess how various combinations of maternal and zygotic AP-2 gene expression might function together to regulate pre- and peri-implantation development. The present study focuses on the interplay between the expression of zygotic Tcfap2aand maternal and zygoticTcfap2c. These studies indicate that zygotic, but not maternal, Tcfap2cexpression is required for normal embryogenesis. In addition, the combined loss of both Tcfap2a and Tcfap2caccelerates embryonic lethality compared to the loss of either gene alone, demonstrating that genetic redundancy exists between these two AP-2 family members during the peri-implantation period of embryogenesis.

Animals↗

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.

Animals↗