Ensuring mitotic fidelity in the early embryo: New actin-based mechanisms
Following fertilization, chromosomes must be accurately segregated into daughter cells with each mitotic division. Yet, pre-implantation embryos display higher rates of aneuploidy compared to somatic cells, which represents a major cause of abnormalities and miscarriage.
Using live-imaging of mitotic divisions in intact-developing embryos, we started to reveal new mechanisms and structures ensuring mitotic fidelity in vivo, which differ from canonical mechanisms used in somatic cells.
In most somatic cells, mitotic chromosomes are primarily organized by the mitotic spindle. Live-imaging 2-cell embryos at high resolution shows that chromosomes cluster and congress before the spindle (orange) is fully assembled.
We uncovered a network of actin cables (orange) inside the cell nucleus in early embryos, prior to mitotic entry and spindle formation.
Nuclear actin forms a network that gathers chromosomes towards the center. This represents a congression-like process, thereby organizing chromosomes before spindle assembly.
Hernandez et al. Actin organizes chromosomes and microtubules to ensure mitotic fidelity in the preimplantation embryo
Science (2025)
Disruption of actin causes multiple mitotic errors (lower panels).
Capturing a mitotic error in real time. A lagging chromosome is mis-segregated producing a micronucleus, which remains separated from the rest after division. This movie was acquired in the intact-developing embryo.
Quantitative tracking shows the actin-driven reduction in chromosome volume.
Live-tracking reveals that key actin nucleators (in this case Formin-2) become diluted from the nuclear region when mitosis starts. This dilution favours actin cable depolymerization, helping to cluster or congress chromosomes towards the center.
Atypical microtubule spindle organization
Mouse embryos initially lack centrosomes and most mitotic spindle lack astral microtubules. The right panel shows a typical anastral spindle. We uncovered a special type of mitotic spindle (left panel) appearing at the 8-cell stage, which displays an aster only on the apical side and is important for segregating the future inner cell mass (ICM) and trophectoderm lineages.
Pomp et al. A monoastral mitotic spindle determining lineage fate and position in the mouse embryo. Nat Cell Biol (2022)