Regulation of asymmetric spindle positioning in the early C. elegans embryo Public Deposited

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  • March 21, 2019
  • McCarthy, Erin Kate
    • Affiliation: College of Arts and Sciences, Department of Biology
  • Asymmetric cell division is necessary for proper development in many organisms, and results in daughter cells of unequal size or cell fate, or both. The first mitotic division of the C. elegans embryo is asymmetric, due to movement of the mitotic spindle to an asymmetric position. While this cell division is a well-studied model of asymmetric spindle positioning, the mechanisms that regulate this event are not completely understood. In order to better understand asymmetric spindle positioning, I have studied microtubule dynamics and the timing of spindle movement during mitosis in the one-cell stage C. elegans embryo. The mitotic spindle of the one-cell stage division shifts towards the posterior cortex of the embryo due to an increase in microtubule pulling forces originating from one side. It is not clear, however, how microtubules contribute to generating the pulling forces required to segregate chromosomes during anaphase in C. elegans. To test this, I monitored the dynamics of kinetochore microtubules through the use of photobleaching and high resolution confocal microscopy. Combined with previous data from other labs, my results suggest that the forces that segregate chromosomes are provided by astral microtubules in early C. elegans embryos, and not by kinetochore microtubules. It is not clear in any developmental system how asymmetric spindle positioning is timed. I found that the mitotic spindle begins to shift at a precise time in the early C. elegans embryo, soon after chromosomes have completed congression to the metaphase plate. This observation suggested an interesting hypothesis—that machinery timing mitotic progression might serve a dual function, also timing asymmetric spindle movement until the appropriate time. Upon manipulation of the cell cycle machinery, my results suggest that components of the spindle checkpoint pathway serve a novel role as a timer for asymmetric spindle positioning in the one-cell C. elegans embryo. This additional role for the spindle checkpoint pathway may ensure that chromosomes attach to the spindle before the spindle shifts to an asymmetric position. This work demonstrates a fundamental new link connecting cell and developmental biology, between mitotic regulation and asymmetric cell division.
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  • In Copyright
  • Goldstein, Robert P.
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  • University of North Carolina at Chapel Hill
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