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Regulated Transcriptional Silencing Promotes Germline Stem Cell Differentiation in Drosophila melanogaster
Başlık:
Regulated Transcriptional Silencing Promotes Germline Stem Cell Differentiation in Drosophila melanogaster
Yazar:
Flora, Pooja, author.
ISBN:
9780438004290
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (193 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 79-10(E), Section: B.
Advisors: Prashanth Rangan Committee members: Melinda Larsen; Ben Szaro; Joseph Wade.
Özet:
Germ cells are the only cell in an organism that have the capacity to give rise to a new organism and are passed from one generation to the next. Therefore, to maintain this unique ability of totipotency and immortality, germ cells execute specific functions, such as, repression of a somatic program and contour a germ line-specific pre- and post-transcriptional gene regulatory landscape. In many sexually reproducing organisms, germ cells are formed during the earliest stages of embryogenesis and undergoes several stages of development to eventually get encapsulated by the somatic cells of the gonad. Once, in the gonad, the germ cells acquire a stem cell fate and some of the encapsulating somatic cells become the stem cell niche which provides structure and signaling to maintain these stem cells. The stem cells over time undergo different stages of development to give rise to healthy gametes that launch the next generation. Therefore, during the life cycle of the germ line critical developmental events need to be tightly monitored for its proper propagation. In my thesis, I aimed to explore two fundamental questions regarding germline stem cell biology: 1) How does a stem cell daughter, which is in close proximity to the stem cell niche, overcome the stem cell program and pushes itself towards a differentiated fate? and 2) How does maternal factors transcribed during female gametogenesis (oogenesis) are effectively deposited to the developing egg even though germ line RNA regulators have a dynamic expression profile during oogenesis.
In the third chapter of my thesis, I show that during Drosophila oogenesis, Pgc mediated transcriptional silencing is required for timely differentiation of germline stem cells (GSC) into gametes. Pgc is expressed in a cell cycle dependent manner in the GSC daughter, also referred to as a cystoblast (CB). In pgc mutants we see an increased number of CBs due to differentiation defects. Pgc targets cell cycle regulators for transcriptional repression, as pgc mutants exhibit an altered cell cycle program. Additionally, the alteration of CB's cell cycle is required for timely deposition of heterochromatin marks. These marks are required for production of piwi interacting RNA (piRNA), which protects the germline genome against transposable elements. Stem cells have an altered cell cycle program and an open chromatin state for their specialized function. These results demonstrate that transcriptional silencing prior to CB differentiation is needed to alter cell cycle and epigenetic landscape to "clear" the stem cell program to ensure proper differentiation.
In the fourth chapter of this thesis I show that pgc is translationally regulated throughout oogenesis and its mode of regulation is shared by a class of germline RNAs. Maternal mRNAs are synthesized during oogenesis to initiate the development of future generations. Some maternal mRNAs are determinants of somatic or germline fate and must be translationally repressed until embryogenesis. However, the translational repressors themselves are also temporally regulated. We find that the 3'UTR of pgc mRNA contains a conserved ten-nucleotide sequence that is bound by different conserved RNA binding proteins (RBPs) at different stages of oogenesis to continuously repress translation except for a brief expression in the stem cell daughter. Pumilio (Pum) binds to this sequence in undifferentiated and early differentiating oocytes and recruits other temporally restricted translational regulators to block pgc translation. After differentiation, Pum levels diminish and Bruno (Bru) levels increase, allowing Bru to bind the same 3'UTR sequence and take over translational repression of pgc mRNA. We have identified a class of maternal mRNAs regulated during oogenesis by both Pum and Bru, including Zelda, activator of the zygotic genome, which contain a sequence similar to the core 10-nt regulatory sequence identified in the pgc 3'UTR. Our data suggests that this hand off mechanism is more generally utilized to inhibit translation of maternal mRNAs during oogenesis.
Notlar:
School code: 0668
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(680415.1) | 680415-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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