Transcription factor AP-2γ is essential in the extra-embryonic lineages for early postimplantation development

Abstract

The members of the AP-2 family of transcription factors play important roles during mammalian development and morphogenesis. AP-2γ (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-2γ 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-2γ, 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-2γ plays no major autonomous role in the development of the embryo proper. By contrast, the presence of AP-2γ in the extra-embryonic membranes is required for normal development of this compartment and also for survival of the mouse embryo.

A genome-wide CRISPR-Cas9 knockout screen identifies essential and growth-restricting genes in human trophoblast stem cells

“…1e ). Amongst the hTSC EGs were several well-established trophoblast regulators, such as TFAP2C 10 , 27 – 31 and TEAD4 32 – 35 , as well as genes without a previously reported association with trophoblast, such as TCAF1 , USP47 , and TSC22D2 (Fig. 1e and Supplementary Fig.…”

The extended analogy of extraembryonic development in insects and amniotes

“…From these, we have identified TFAP2A/Tfap2a, TFAP2C/Tfap2c, DLX5/Dlx5 and GATA3/Gata3 as markers of amniotic ectoderm in Homo and Mus as well as in Gallus [80,81]. However, these factors do not seem to cause a phenotype in the amniotic ectoderm when deleted in Mus [82–85], perhaps owing to redundancy with other family members. DLX5 does not have a clear orthologue in Tribolium (table 2), and the expression of Tc-AP2 (orthologue of TFAP2A ) has not been investigated.…”

Transcription factor networks in trophoblast development

“…Even though disputed by some [ 65 ], this in vitro system was used to demonstrate that the network of TFs GATA2, GATA3, TFAP2A and TFAP2C regulates trophoblast identity and facilitates the exit from pluripotency, and depletion of GATA3 prevents specification of trophoblast identity [ 66 ]. The critical roles of GATA2, GATA3 and TFAP2C in the human CTB and hTSCs are expected, as their depletion in the mouse system resulted in impaired trophoblast development resulting in embryonic lethality [ 62 , 67 ]. Moreover, GATA2 and TFAP2C gained further prominence, as depletion of either impaired reprogramming of fibroblasts to naïve hESCs, which have the potential to adopt the hTSC state in suitable media conditions [ 68 ].…”