Biology subjects

Timmers, E.

Publications and source records attributed to Timmers, E..

3 recordsLinked to original sources

bioRxiv2026

Wnt signalling controls abscission dynamics in mouse embryonic stem cells

Cell division is a crucial process that ensures proper development of multicellular organisms. Cell division ends in abscission, a process in which the intercellular bridge between two sister cells is cut. Although abscission usually happens shortly after chromosome segregation, abscission is severely delayed in mouse embryos and embryonic stem cells (mESC). The regulation of the duration of abscission influences cell fate transitions but how cell state and abscission dynamics crosstalk remains unknown. Here, we show that a key pluripotency pathway, the Wnt signalling pathway, controls abscission dynamics. Upon deactivation of Wnt signalling in naive mESCs, abscission becomes faster. Wnt signalling regulates abscission dynamics in mESCs through two mechanisms. First, Wnt signalling keeps the amount of Aurora B high at the intercellular bridge, probably by preventing Aurora B degradation. In turn, high Aurora B activity at the bridge delays bridge abscission. Second, a key component of Wnt signalling, the kinase GSK-3{beta} localizes at the intercellular bridge with microtubules and their associated proteins (MAPs). In pluripotent cells, inactivation of GSK-3{beta} leads to an increase of stable microtubules at the bridge stable which causes delayed abscission. Crucially, inhibition of GSK-3{beta} after cells have exited naive pluripotency accelerates abscission, demonstrating that cell state influences the output of the abscission signalling pathway. The permissive function of canonical Wnt on cell state is thought to be mediated by reinforcement of existing pluripotency network; altogether, our work shows that non-canonical Wnt is also context dependent.

cell biology↗

bioRxiv2025

Scaling of mouse somitogenesis by coupling of cell cycle to segmentation clock oscillations

While scaling developmental processes is fundamental to maintaining robust tissue patterning, the mechanisms underlying this process are enigmatic. Somitogenesis, the periodic segmentation of growing mesodermal tissue in vertebrate embryos1, involves precise scaling with the unsegmented presomitic mesoderm (PSM) over developmental time and under perturbation2-4. Somitogenesis is spatiotemporally regulated by FGF and Wnt morphogen gradients and the segmentation clock -- oscillations in Notch, Wnt, and FGF signalling5-7. Here, we find that cell proliferation is distributed throughout the oscillating PSM. Long-term single-cell tracking in mouse embryo tails uncovered a correlation between cell cycle progression and the segmentation clock, with microfluidics-based entrainment indicating coupling between the cell cycle and signalling oscillations, likely through S-phase inducing Cyclins. A theoretical model suggests this coupling ensures uniform PSM growth, uniform morphogen dilution and precise somite formation, which we validated experimentally by blocking cell proliferation. Our findings reveal that coupling cell proliferation to signalling oscillations is crucial for robust somitogenesis and precise somite scaling.

developmental biology↗

bioRxiv2020

SPEN is Required for Xist Upregulation during Initiation of X Chromosome Inactivation

At initiation of X chromosome inactivation (XCI), Xist is monoallelically upregulated from the future inactive X (Xi) chromosome, overcoming repression by its antisense transcript Tsix. Xist recruits various chromatin remodelers, amongst them SPEN, which are involved in silencing of X-linked genes in cis and establishment of the Xi. Here, we show that SPEN plays an important role in the initiation of XCI. Spen null female mouse embryonic stem cells (ESCs) are defective in Xist upregulation upon differentiation. We find that Xist-mediated SPEN recruitment to the Xi chromosome happens very early in XCI, and that SPEN-mediated silencing of the Tsix promoter is required for Xist upregulation. Accordingly, failed Xist upregulation in Spen-/- ESCs can be rescued by concomitant removal of Tsix. These findings indicate that SPEN is not only required for the establishment of the Xi, but is also crucial in the initiation of the XCI process.

developmental biology↗