Effects of numerical centrosome aberrations on cell division and mitotic spindles
Abstract/Contents
- Abstract
- Most cycling animal cells contain one or two centrosomes depending on cell cycle stage. However, alternative centrosome states are crucial to who we are: We all come from an mother cell lacking centrosomes, the acentrosomal human oocyte, which, after fertilization, developed into a conceptus that invaded the maternal endometrium using trophoblast giant cells containing more than two centrosomes. However, while numerical centrosome aberrations occur as physiological phenomena, they can also occur pathologically, such as in tumorigenesis and microcephaly. Centrosomes are non-membrane-bound organelles that are in the cytosol of most cycling animal cells and are major microtubule organizing centers during mitosis. During mitosis, one centrosome consisting of two centrioles and surrounding pericentriolar material (PCM) is present at each side of the mitotic spindle apparatus, which separates chromosomes into two future daughter cells. In late G2 and early mitosis, centrosomes undergo a PCM expansion that increases the capacity to nucleate and organize microtubules. The two centrosomes then become separated, defining the spindle poles. However, cells can build bipolar spindles and divide into two without centrosomes or with extra centrosomes. Nevertheless, numerical centrosomes aberrations, whether greater or less than two during mitosis, influence the progression and, in some cases, outcome of cell division. In absence of centrosomes mitotic duration becomes elongated and PCM proteins localize to the spindle poles. In presence of supernumerary centrosomes, multiples spindle poles can form and either become clustered into two poles, resulting in bipolar division, or remain as multiple poles, resulting in multipolar division. After a brief introduction to centrosomes and numerical centrosome aberrations in Chapter 1, I present an experimental analysis of cell division in mammalian cells without centrosomes (Chapters 2-3) or with supernumerary centrosomes (Chapter 4). In Chapter 2, I investigate the cause of the mitotic elongation in acentrosomal cells and specifically assess whether the spindle assembly checkpoint, which halts mitotic progression until chromosomes are correctly attached to the mitotic spindle, is responsible for this elongation. Furthermore, I assess whether the temporal delay is necessary for completion of cell division in acentrosomal cells. In Chapter 3, I investigate the spatiotemporal arrangement of normally centrosome-localized proteins, with focus on the PCM proteins γ-tubulin and Cep192, during mitosis in absence of centrosomes. In Chapter 4, I investigate how cells with supernumerary centrosomes return to homeostatic centrosome numbers on a population level. In Chapter 5, I present general conclusions as well as ideas for future investigation of numerical centrosome aberrations in mammalian cells.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2022; ©2022 |
| Publication date | 2022; 2022 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Farrell, Kacie |
|---|---|
| Degree supervisor | Stearns, Tim |
| Thesis advisor | Stearns, Tim |
| Thesis advisor | Feldman, Jessica L |
| Thesis advisor | O'Brien, Lucy Erin, 1970- |
| Thesis advisor | Shen, Kang, 1972- |
| Degree committee member | Feldman, Jessica L |
| Degree committee member | O'Brien, Lucy Erin, 1970- |
| Degree committee member | Shen, Kang, 1972- |
| Associated with | Stanford University, Department of Biology |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | KC Farrell. |
|---|---|
| Note | Submitted to the Department of Biology. |
| Thesis | Thesis Ph.D. Stanford University 2022. |
| Location | https://purl.stanford.edu/pw130yn3797 |
Access conditions
- Copyright
- © 2022 by Kacie Farrell
- License
- This work is licensed under a Creative Commons Attribution 3.0 Unported license (CC BY).
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