Cells divide to create two daughter cells through cytokinesis. Daughter cells of different sizes are created by shifting the position of the cleavage furrow. The cleavage furrow forms at the position of the metaphase plate so in asymmetric cytokinesis the spindle is shifted towards one pole. Unlike most systems, Drosophila neuroblasts have a centrally localized metaphase plate but divide asymmetrically. Drosophila neuroblasts divide asymmetrically due to the presence of a polarized myosin domain at the basal pole during mitosis. I investigated the mechanism by which the basal myosin domain produces asymmetric cytokinesis and the pathway regulating this domain.
We tested several mechanisms by which the basal myosin domain could lead to asymmetric cytokinesis. Based on surface area and volume measurements, I demonstrated that asymmetric addition of new membrane is not involved. I determined that neuroblasts exhibit asymmetric cortical extension during anaphase with the apical pole extending 2-3 times more than the basal pole. Mutants that lose basal myosin extend equally at both poles supporting this model. Mutants that retain apical myosin exhibited symmetric cortical extension but still divided asymmetrically, demonstrating that asymmetric cortical extension is not required for asymmetric cytokinesis. Observations of the mitotic spindle show that the cleavage furrow forms at a position biased towards the basal pole when compared to the position of the metaphase plate even though this position is still equidistant between the centrosomes. I observed that midzone components shift basally in a basal domain dependent manner suggesting that contraction of the basal domain leads to new microtubule-cortex interactions at a position away from the spindle midzone.
I demonstrated that the basal domain is regulated by the heterotrimeric G protein, Gβ13F, which is activated by Pins. In Gβ mutants, the localization of all basal components (myosin, anillin, and pavarotti) is lost and the cells divide symmetrically. Although the basal domain is contiguous with equatorial myosin, it is not regulated by the same pathway and photobleaching experiments indicate that they exhibit different behaviors during anaphase suggesting a difference in temporal regulation.
This dissertation includes previously published coauthored material.
| Identifer | oai:union.ndltd.org:uoregon.edu/oai:scholarsbank.uoregon.edu:1794/13000 |
| Date | 11 July 2013 |
| Creators | Connell, Marisa |
| Contributors | Prehoda, Kenneth |
| Publisher | University of Oregon |
| Source Sets | University of Oregon |
| Language | en_US |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Rights | All Rights Reserved. |
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