Physics of the Early Embryonic Divisions Workshop – Microtubules, energy and cell fate decisions in early embryogenesis

Text written by Olga Afonso, Helena Cantwell, and Shuzo Kato

Microtubules: bridging meiosis to mitosis and cellular differentiation 

In a workshop dedicated to early embryonic divisions, we could not miss a session focused on microtubules. The session started with a talk from Helena Cantwell (University of California, Berkeley) who combined two model systems, Ciona robusta and Xenopus laevis to study the molecular mechanisms that mediate the meiotic to mitotic spindle transition. Helena found that Casein Kinase II is as a key regulator of spindle morphology that acts through the Ran-GTP pathway of spindle assembly [1]. Further work on how the Ran-GTP gradient itself changes during the meiotic to mitotic spindle transition would ultimately close the loop. Simone Reber, from the Max-Planck Institute for Infection Biology, showed recent work from the lab, focused on the changes of spindle morphology during cell differentiation. They used optical diffraction tomography to show that differentiated cells have a more dilute cytoplasm resulting in a shift of microtubule mass from the mitotic spindle bulk to centrosomes and astral microtubules [2]. Remaining questions relate to how the cytoplasm is diluted during differentiation and what the biological function of increased astral microtubules is. The session concluded with a presentation from Nicolas Minc, Institute Jaques Monod, Paris. Nicolas Minc uses sea urchin embryos to study how the position of the metaphase spindle is maintained in a large cell, where microtubules are far away from the cell’s boundary. By using a combination of optical tweezers and computational analysis of cytoplasmic flows, Nicolas showed that spindle positioning is maintained by the viscoelastic properties of the cytoplasm [3,4,5]. Overall, this session covered the role of microtubules in every step of embryonic development: from the very first meiosis to mitosis transition to what happens to the spindle morphology when cells start to differentiate.

Energetics of early development

Cellular processes in embryonic development are powered by energy metabolism. Although the biochemical pathways of metabolism have been characterised in past centuries, how embryos organise limited energy sources for their accurate development is poorly understood [6,7]. Specifically, what are the energetic costs of specific processes such as cytoskeletal assembly and cell cycle regulation? Also, how do intracellular energy fluxes constrain these processes? And, what kind of quantitative tools do we need to measure or infer energy fluxes in development? Qiong Yang (the University of Michigan) addressed these questions by quantifying how energy sources limit spatiotemporal control of the cell cycle in embryos using Xenopus laevis cytoplasmic extracts. Shuzo Kato (TU Dresden) discussed the role of energy fluxes in regulating mitotic spindle organisation using cell-free and embryo systems. Jonathan Rodenfels (the Max Planck Institute of Molecular Cell Biology and Genetics) shared insights into the spatial control of energy metabolism during development, and the possible role energetics play in evolution. Assessing these challenges and questions will advance our understanding of the energetic basis of embryonic development.

Cell fate decisions in early embryos

The focus of the workshop then shifted to cellular differentiation with a group of talks describing work tackling the question of what drives cell fate decisions in early embryos using a range of different systems and approaches. Silvia Santos (The Francis Crick Institute) discussed her lab’s work exploring the interplay between cell cycle signature and cell fate in embryonic stem cells (ESCs) and ESC-based organoid models [8]. Amber Rock (Harvard University) then presented her work using acoel worms [9] to explore the minimum components required for, and contribution of positional information to, viable embryonic development. Jordi Garcia-Ojalvo (Universitat Pompeu Fabra) finished the session with a discussion of his group’s work using physical approaches, in combination with experimental data, to uncover circuits driving cell fate specification in embryogenesis [10]. This session brought together a range of perspectives from experimental embryology and cell biology to modelling based on physical principles and sparked interesting discussions around cell autonomy, identity and decision making in the context of embryogenesis.

Early embryonic cell division is a complex phenomenon involving both physical and biological processes. Overall, the workshop was truly a unique opportunity to sit at the same table established group leaders in the field of early embryonic divisions and young researchers in a relaxed and informal setting that fostered open discussions on longstanding and emerging problems, as well as collaborations across traditional disciplines. Moreover, the meeting gathered experimentalists and theoreticians, a much-needed synergy to tackle complex challenges in the field. As an emerging property of such collaborative atmosphere, we built a robust network among all participants – a network that will undoubtedly strengthen the “early embryo” research community. Exciting times lie ahead, as we uncover the principles of early embryonic development.

References

[1] Cantwell H, Nguyen H, Kettenbach A, Heald R. Spindle morphology changes between meiosis and mitosis driven by CK2 regulation of the Ran pathway. Biorxiv (2024) DOI: 10.1101/2024.07.25.605073.

[2] Kletter T, Muñoz O, Reusch S, Biswas A, Halavatyi A, Neumann B, Kuropka B, Zaburdaev V, Reber S. Cell State-Specific Cytoplasmic Material Properties Control Spindle Architecture and Scaling. Biorxiv (2024) DOI: 10.1101/2024.07.22.604615

[3] Nommick A, Xie J, Minc N. Manipulation of Spindle Position Using Magnetic Tweezers in Sea Urchin Embyos. Methods Mol Biol. (2025) 2872:87-100.

[4] Tanimoto H, Sallé J, Dodin L, Minc N. Physical Forces Determining the Persistency and Centering Precision of Microtubule Asters. Nat Phys. (2018) 14(8):848-854.

[5] Najafi J, Dmitrieff S, Minc N. Size- and position-dependent cytoplasm viscoelasticity through hydrodynamic interactions with the cell surface. PNAS (2023) 120(9)e2216839120.

[6] Ghosh S, Körte A, Serafini G, Yadav V, Rodenfels J, Developmental energetics: Energy expenditure, budgets and metabolism during animal embryogenesis. Semin. Cell Dev. Biol. (2023) 138, 83–93.   

[7] Yang X, Heinemann M, Howard J, Foster P, Physical bioenergetics: Energy fluxes, budgets, and constraints in cells. PNAS (2021) 118(26)e2026786118.   

[8] Padgett J, Santos S. From clocks to dominoes: lessons on cell cycle remodelling from embryonic stem cells. FEBS letters (2020) 594(13), 2031-2045.

[9] Srivastava M. Studying development, regeneration, stem cells, and more in the acoel Hofstenia miamia. Curr. Top. Dev. Biol. (2022) 147:153–172.

[10] Saiz N, Mora-Bitria L, Rahman S, George H, Herder J, Garcia-Ojalvo J, Hadjantonakis, AK. Growth Factor-Mediated Coupling between Lineage Size and Cell Fate Choice Underlies Robustness of Mammalian Development. eLife (2020) 9, e56079.

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