A computer simulation of a simple exclusion model faithfully recapitulated wildtype and mutant spindle position phenotypes support a volume exclusion model for positioning acentriolar meiotic spindles.
Abstract
Cortical positioning of oocyte meiotic spindles is required for reducing chromosome number by segregating chromosomes into polar bodies. In C. elegans, kinesin-1 transports membrane-bound organelles inward into a central ball that is hypothesized to push the meiotic spindle outward. Using focused ion beam scanning electron microscopy, we found that the percent volume occupied by membrane-bound organelles was 28% in a mature oocyte that has completed endocytosis of the yolk precursor, vitellogenin, compared to 17% in a less mature oocyte that has not yet endocytosed vitellogenin. We therefore hypothesized that blocking endocytosis of vitellogenin would reduce the size of the central ball of organelles packed inward by kinesin-1 and limit outward movement of the spindle. Depletion of vitellogenin or proteins required for endocytosis resulted in a smaller central volume of kinesin-coated organelles and defective spindle positioning. A computer simulation of a simple exclusion model faithfully recapitulated wildtype and mutant spindle position phenotypes. These results support a volume exclusion model for positioning acentriolar meiotic spindles.
Accurate chromosome segregation depends on the formation of a functional bipolar spindle. While somatic cells rely on centrosomes to organize spindle assembly, mammalian oocytes lack canonical centrosomes and must assemble their meiotic spindles through acentrosomal mechanisms. Following fertilization, embryos progress...
Yolk-cytoplasm segregation is among the earliest spatial organization events in the developing embryo of many oviparous animals. The segregation process is intimately linked to early embryonic cleavage and pattern formation, and exhibits a wide range of spatial and temporal diversity. However, the underlying cytoskelet...
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While regulation of spindle positioning and orientation is known to be mediated by cortical pulling forces generated by dynein on astral microtubules, the contribution of microtubule-based pushing forces remains less clear. We developed a two-dimensional computational model that incorporates both cortical pulling and m...
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The spindle assembly checkpoint (SAC) monitors kinetochore-microtubule interactions to ensure accurate chromosome segregation. In mitosis, investigation of its silencing at anaphase centers on whether attachment or tension is the key signal, while in meiosis for mammalian oocytes it remains unclear whether centromere...
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