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Partitioning the Cytoplasm in the C. elegans Zygote
Başlık:
Partitioning the Cytoplasm in the C. elegans Zygote
Yazar:
Wu, Youjun, author.
ISBN:
9780438010352
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (206 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 79-10(E), Section: B.
Advisors: Erik E. Griffin Committee members: Amy S. Gladfelter; Erik E. Griffin; James B. Moseley; Jeremy F. Nance.
Özet:
Asymmetric cell divisions are essential for the generation of cell diversity and for the maintenance of tissue homeostasis. One hallmark of most asymmetric cell divisions is the segregation of cortical and cytoplasmic factors along the cell polarity axis, such that they are asymmetrically inherited by the two daughter cells, which gives rise to differences in daughter cell fate. Despite the advances in understanding how cortical factors are segregated during asymmetric cell divisions, relatively little is known about how the partitioning of cytoplasmic factors is controlled. During the first asymmetric cell division of the C. elegans zygote, a collection of RNA-binding proteins form opposing concentration gradients along the anterior/posterior axis in response to the conserved polarity regulators, the PAR proteins. MEX-5/6 form anterior-rich concentration gradients that drive the segregation of PIE-1, POS-1 and MEX-1 to form posterior-rich gradients. Concurrently, phase-separated RNA/protein granules called P granules become highly enriched in the posterior cytoplasm.
In this dissertation, I use a range of quantitative live-cell imaging techniques combined with genetic manipulations and mathematical modeling to understand the reaction-diffusion mechanisms that partition the cytoplasmic proteins in the C. elegans zygote. We find that MEX-5/6 act downstream of PAR polarities to control the segregation of PIE-1, POS-1 and MEX-1 through local control of their mobility, and that there is a direct coupling between MEX-5/6 concentration and PIE-1 mobility. Using single particle tracking, we find that MEX-5 and PIE-1 rapidly switch between a uniform fast-diffusing state and an asymmetric slow-diffusing state. MEX-5 preferentially switches to the slow-state in the anterior in response to posterior PAR-1 activity, leading to the accumulation of MEX-5/6 in the anterior. In turn, high concentrations of MEX-5/6 prevent the switch of PIE-1 from a fast- to a slow-diffusing state, thereby causing the retention of PIE-1 in the posterior.
We extended our analysis to MEG-3, a P granular protein that forms a posterior-rich concentration gradient in response to MEX-5/6 and is required for P granule segregation. Surprisingly, single molecule imaging of MEG-3 suggests that the MEG-3 gradient does not contribute to P granule segregation but is rather a separate consequence of regulation from upstream factors.
Notlar:
School code: 0059
Tüzel Kişi Ek Girişi:
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(682003.1) | 682003-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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