Maternal‐effect gene Ces5/Ooep/Moep19/Floped is essential for oocyte cytoplasmic lattice formation and embryonic development at the maternal‐zygotic stage transition

Abstract

In a search for genes specifically expressed in mouse embryonic stem cells, we identified one we called Ces5. We found that it corresponded to the Ooep gene, which was recently reported to be expressed specifically in oocytes. Mouse Ces5/Ooep, also called Moep19 or Floped, encoded a 164-amino acid protein, which was detected in the cytoplasm of developing and mature oocytes and in embryos throughout the preimplantation period. To examine its function, we carried out targeted disruption of this gene. The Ces5/Ooep-null mice were grossly normal, but the females were infertile. Although the ovaries and ovulation appeared normal, the embryos from Ces5/Ooep-null females mated with wild-type males showed developmental arrest at the two- or four-cell stage. In addition, their first cleavage was considerably delayed and often asymmetrical. Thus, Ces5/Ooep is a maternal-effect gene. By electron microscopy, we found that the eggs from Ces5/Ooep-null females lacked oocyte cytoplasmic lattices (CPLs), which have long been predicted to function as a storage form for components that are maternally contributed to the early embryo. Further analysis showed that CES5/OOEP was directly associated with the CPLs. These results indicate that CES5/OOEP is an essential component of the CPLs and is required for embryonic development at the maternal-zygotic stage transition.

The subcortical maternal complex: multiple functions for one biological structure?

“…Indeed, the absence of TLE6 prevents the formation of the cytoplasmic F-actin fine meshwork in the murine zygote subcortex and leads to asymmetric cell division and cleavage-stage embryonic death. The interaction of TLE6 with the F-actin meshwork occurs through Cofilin [14], a known regulator of actin cytoskeleton that centrally positions the spindle in mouse zygotes [23]. Together, these findings show that the SCMC controls spindle formation and positioning through the cytoplasmic F-actin meshwork in mouse zygotes and clarify why its presence is required for proper symmetric cell division.…”

“…Null mutations of the single-copy genes encoding MATER, FLOPED, or TLE6 result in cleavage-stage embryonic arrest and female sterility [4,10,14]. The absence of Filia has a more subtle phenotype with delayed preimplantation development and decreased fecundity [15].…”

“…The absence of Filia has a more subtle phenotype with delayed preimplantation development and decreased fecundity [15]. The presence of MATER, FLOPED, or TLE6 (but not FILIA) is required for the formation of the SCMC [10,14,15].…”

“…The analysis of the TLE6 null phenotype [14] led to the identification of the first and unique demonstrated function of the SCMC. Indeed, the absence of TLE6 prevents the formation of the cytoplasmic F-actin fine meshwork in the murine zygote subcortex and leads to asymmetric cell division and cleavage-stage embryonic death.…”

“…The proteins that contribute to the SCMC are encoded by maternal effect genes (MEGs) [4,10,14,15]. MEGs code for a special class of maternal transcripts required for early cleavage events post fertilization [6,15].…”