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Understanding the Mechanisms of Chromosome and Spindle Dynamics during Meiosis in Caenorhabditis elegans Oocy
Başlık:
Understanding the Mechanisms of Chromosome and Spindle Dynamics during Meiosis in Caenorhabditis elegans Oocy
Yazar:
Torre-Santiago, Keila Margarita, author.
ISBN:
9780438115804
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (192 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 79-11(E), Section: B.
Advisors: Sarah M. Wignall Committee members: Erik Anderson; Richard Morimoto; Xiaozhong Wang.
Özet:
In this dissertation, I detail new mechanisms for acentrosomal spindle assembly and chromosome dynamics during C. elegans oocyte meiosis. Investigating oocyte meiosis is imperative, as a detailed understanding is necessary in order to potentially extend the window of female fertility and meaningfully improve the genetic outcomes of children. Using C. elegans as an instrument for discovery, I sought to understand how acentrosomal spindles formed and how chromosomes were properly segregated in this unique mode of cell division.
When I began this work, it was known that C. elegans oocytes had a very unique spindle structure, where lateral microtubule bundles---instead of the canonical kinetochore-microtubule attachments---mediated chromosome movements in congression and that a plus-end-directed motor protein, KLP-19, drove these movements. Shortly thereafter, it was published that chromosome segregation in this system was independent of kinetochores, suggesting the existence of an entirely new method of dividing genetic material.
Many questions regarding this new mechanism needed to be answered. First, given that a plus-end motor protein played a key role in driving chromosome movement, are there other forces operating on the chromosomes? Does a minus-end motor also contribute to chromosome movements in this specialized spindle? I sought to answer this question by assessing the role of the minus-end motor dynein in chromosome congression and segregation. I found that chromosome dynamics along lateral microtubule bundles are powered by a tug-of-war between opposing motor forces, KLP-19 and dynein. In metaphase, dynein begins accumulating on the chromosomes, where it is elegantly counterbalanced by KLP-19. Upon anaphase onset, however, KLP-19 is left at the metaphase plate, allowing dynein to fully take over and drive chromosome movement back to spindle poles along the lateral microtubule bundles, much like a train along a track. This method of chromosome segregation is entirely novel and it represents a significant departure from canonical cell division.
Once these discoveries were made, I next sought to reveal how the spindle was organized, and how the lateral microtubule bundles were regulated. To answer this question, I launched studies of MCAK, a microtubule depolymerizing kinesin, known to play key roles in mitotic spindle regulation. Following this line of inquisition, I found multiple roles for MCAK: I established that MCAK has a role in global regulation of microtubule length in the oocyte. Importantly, I determined that MCAK is responsible for helping establish proper bipolar spindle formation, and later preserving this unique configuration. MCAK achieves this by actively restricting the length of microtubules at the spindle center, from its location in the midbivalent ring. Finally, I also uncovered a role for MCAK in anaphase, where it is responsible for keeping the microtubule channels open and unobstructed as chromosomes segregate.
In pursuit of these larger questions, I also delved into super-resolution imaging, which led to a detailed characterization of a system that was previously poorly understood. I found that the metaphase spindle has a very short overlap zone. I also determined that lateral microtubule bundles persist until the end of anaphase. Finally, I was able to characterize the physical aspects of the midbivalent ring, in a way that conventional fluorescent microscopy had not yet been able to do.
Together, these findings significantly contribute to our understanding of how the unique acentrosomal structure is initially established, how it is regulated, and how it facilitates the proper partitioning of genetic material without centrosomes or kinetochores. These studies provide a more comprehensive picture of the mechanisms underpinning proper chromosome division in female meiosis in C. elegans, which will serve to inform meiosis models in other organisms as well.
Notlar:
School code: 0163
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(687597.1) | 687597-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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