Institut Jacques Monod Seminars – Lendert Gelens

Invité par l’équipe Wassmann, Lendert Gelens (Laboratory of Dynamics in Biological Systems, University of Leuven, Belgium) présentera un séminaire de l’Institut Jacques Monod sur le thème :

Nuclei coordinate the cell cycle in space and time

Résumé :

Proliferating cells replicate their DNA and components before dividing, but how subcellular localization impacts cell cycle timing remains unclear. Using frog egg extracts encapsulated in droplets, we studied cell cycle oscillations with and without nuclei [1]. Time-lapse microscopy revealed that nuclei increase cell cycle duration, with increasing nuclear volume correlating with longer periods across different Xenopus species. This relationship persisted without DNA replication or transcription but was disrupted by inhibiting nuclear import or Wee1 kinase. A computational model incorporating nuclear-cytoplasmic compartmentalization and periodic nuclear envelope dynamics reproduced these findings, linking nuclear size to cycle timing. These results explain the lengthening of the cell cycle at the midblastula transition when cells become smaller, and the nuclear-cytoplasmic ratio increases.

In early Xenopus embryos (~1.2 mm), mitotic waves coordinate the cell cycle over long distances, as diffusion alone is insufficient. Using X. laevis egg extracts and a Cdk1 FRET sensor, we observed a transition from phase to trigger wave dynamics in initially homogeneous cytosol [2]. Spatial heterogeneity and nuclei accelerated this transition, while metaphase-arrested extracts induced an immediate shift. Simulations revealed transient phase waves as trigger waves required time to entrain the system. Both wave types emerge as part of a unified process for coordinating the cell cycle across large distances.

[1] Pineros, L. *; Frolov, N. *; Ruiz-Reynés, D.; Eynde, A. Van; Cavin-Meza, G.; Heald, R.; Gelens, L.; The nuclear-cytoplasmic ratio controls the cell cycle period in compartmentalized frog egg extract; BioRxiv, 2024.

[2] Puls*, O.; Ruiz-Reynés*, D.; Tavella, F.; Jin, M.; Kim, Y.; Gelens*, L.; Yang*, Q.; Spatial heterogeneity accelerates phase-to-trigger wave transitions in frog egg extracts; Nature Communications, vol. 15, no. 10455, 2024.