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<p>During embryogenesis, the first cell fate decision—whether the cell participates in development of the embryo or not—is often linked to the positioning of the nucleus. The cell cycle oscillator and associated cytoskeletal dynamics contribute to the control of nuclear positioning. However, the mechanisms that ensure that the correct number of nuclei move to their appropriate place remain poorly understood. Here we show that the orientation of the mitotic spindle controls the first fate decision, embryonic or yolk cell fate, in <i>Drosophila</i> embryos using light sheet microscopy experiments. Combining computational methods inspired by integral geometry, manipulation of cell cycle genes, and investigation of the relationship between geometry and topology, we show that spindle orientation is controlled by topological interactions with neighbouring nuclei and not by internuclear distance. Leveraging the physics of space-filling systems, we develop a theory for topological dependency in microtubule structures. Our work shows how the topological interplay of microtubule mechanics can ensure robust control of nuclear density and determine cell fate.</p>

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Topological interactions drive the first fate decision in the Drosophila embryo

  • 期刊论文

  • 发表日期：

    2025年2月25日

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  • Woonyung Hur,
  • Arghyadip Mukherjee,
  • Luke Hayden,
  • Ziqi Lu,
  • Anna Chao,
  • Noah P. Mitchell,
  • Sebastian J. Streichan,
  • Massimo Vergassola,
  • Stefano Di Talia

摘要

During embryogenesis, the first cell fate decision—whether the cell participates in development of the embryo or not—is often linked to the positioning of the nucleus. The cell cycle oscillator and associated cytoskeletal dynamics contribute to the control of nuclear positioning. However, the mechanisms that ensure that the correct number of nuclei move to their appropriate place remain poorly understood. Here we show that the orientation of the mitotic spindle controls the first fate decision, embryonic or yolk cell fate, in Drosophila embryos using light sheet microscopy experiments. Combining computational methods inspired by integral geometry, manipulation of cell cycle genes, and investigation of the relationship between geometry and topology, we show that spindle orientation is controlled by topological interactions with neighbouring nuclei and not by internuclear distance. Leveraging the physics of space-filling systems, we develop a theory for topological dependency in microtubule structures. Our work shows how the topological interplay of microtubule mechanics can ensure robust control of nuclear density and determine cell fate.