Post-transcriptional control of gene expression in mouse early embryo development: a view from the tip of the iceberg

Abstract

Fertilization is a very complex biological process that requires the perfect cooperation between two highly specialized cells: the male and female gametes. The oocyte provides the physical space where this process takes place, most of the energetic need, and half of the genetic contribution. The spermatozoon mostly contributes the other half of the chromosomes and it is specialized to reach and to penetrate the oocyte. Notably, the mouse oocyte and early embryo are transcriptionally inactive. Hence, they fully depend on the maternal mRNAs and proteins stored during oocyte maturation to drive the onset of development. The new embryo develops autonomously around the four-cell stage, when maternal supplies are exhausted and the zygotic genome is activated in mice. This oocyte-to-embryo transition needs an efficient and tightly regulated translation of the maternally-inherited mRNAs, which likely contributes to embryonic genome activation. Full understanding of post-transcriptional regulation of gene expression in early embryos is crucial to understand the reprogramming of the embryonic genome, it might help driving reprogramming of stem cells in vitro and will likely improve in vitro culturing of mammalian embryos for assisted reproduction. Nevertheless, the knowledge of the mechanism(s) underlying this fundamental step in embryogenesis is still scarce, especially if compared to other model organisms. We will review here the current knowledge on the post-transcriptional control of gene expression in mouse early embryos and discuss some of the unanswered questions concerning this fascinating field of biology.

Figure 1

Schematic representation of the changes occurring in the chromatin of the zygote. The blastomeres of the two-cell embryo are the first truly totipotent cells. They originate from two transcriptionally repressed cells and acquire their peculiar capacity through the changes occurring in the zygote. The main necessary modifications concerning the remodeling of the chromatin of the two parental genomes are: erasure of the epigenetic marks that typify the genome of gametes; maintenance of epigenetic marks in the imprinted genes. This extensive reprogramming is carried out by the maternal factors stored in the oocyte.

Figure 2

Maternal mRNAs are accumulated during oogenesis and bound by proteins in complexes called RNPs (ribonucleoproteins). Maternal mRNAs are stored in an inactive masked state until recruited for translation in a stage-specific manner. Soon after fertilization maternal RNAs are loaded onto polysomes for translation, in order to provide essential factors to the newly formed zygote, before the full activation of its genome occurs. At the two-cell stage 90% of the maternal transcripts will be degraded. The starting point for timing (hours) is fertilization.