Preimplantation Development and Gene Regulatory Mechanisms in Mouse Embryos

Preimplantation development in the mouse encompasses the critical interval from fertilisation to blastocyst formation, during which a single totipotent zygote gives rise to distinct lineages and establishes the foundation for embryo implantation. This period is marked by dramatic transitions in gene expression, epigenetic reprogramming and chromatin architecture. The maternal-to-zygotic transition initiates a handover from stored maternal RNAs and proteins to newly synthesised zygotic transcripts, a process regulated by histone modifications, chromatin remodellers and sequence-specific transcription factors. Concurrently, the emergence of higher-order chromatin organisation, including the establishment of topologically associating domains, guides lineage-specific gene activation. Spatial and temporal control of transcription factors such as MYC, STAT3 and key kinases ensures orderly progression through the one-cell to two-cell stages, while histone variants and covalent modifications sculpt chromatin accessibility. Environmental inputs, including culture conditions and sperm treatment, can alter epigenetic trajectories with lasting effects on gene expression and developmental competence. Together, these interwoven regulatory mechanisms underlie the remarkable plasticity of early embryos and inform strategies for assisted reproductive technologies, lineage derivation and regenerative medicine.

Research from Nature Portfolio

Recent studies have demonstrated the essential role of the MYC–MAX heterodimer in driving major zygotic genome activation at the late two-cell stage. Inhibition of MYC function during this window arrests embryos at two cells by suppressing the onset of zygotic transcription, revealing a stage-specific requirement for MYC in establishing totipotency and subsequent preimplantation progression. This finding underscores the pivotal interplay between sequence-specific transcription factors and the wave of genome-wide transcription that inaugurates embryonic control of development.

Preimplantation Development and Gene Regulatory Mechanisms in Mouse Embryos publication trend

The graph below shows the total number of articles in preimplantation development and gene regulatory mechanisms in mouse embryos across all publications each year (not limited to Nature Index journals).

Technical terms

Zygotic genome activation (ZGA): The onset of transcription from the embryonic genome, marking the shift from maternal to zygotic control of development.

Maternal-to-zygotic transition (MZT): The coordinated process of maternal mRNA clearance and initiation of zygotic transcription during early embryogenesis.

Chromatin remodelling: ATP-dependent repositioning or restructuring of nucleosomes to regulate DNA accessibility for transcription, replication and repair.

Histone variant: A non-canonical histone protein that replaces standard histones in the nucleosome, influencing chromatin structure and function.

Topologically associating domain (TAD): A self-interacting chromosomal region within which regulatory elements and genes preferentially interact to coordinate gene expression.

References

1. H3.1/3.2 regulate the initial progression of the gene expression program. Nucleic Acids Research (2024).
2. MYC–MAX heterodimerization is essential for the induction of major zygotic genome activation and subsequent preimplantation development. Scientific Reports (2023).
3. Sperm Energy Restriction and Recovery (SER) Alters Epigenetic Marks during the First Cell Cycle of Development in Mice. International Journal of Molecular Sciences (2022).
4. Maternal Prkce expression in mature oocytes is critical for the first cleavage facilitating maternal‐to‐zygotic transition in mouse early embryos. Cell Proliferation (2022).