Conserved regulation of the switch from proliferation to differentiation in the germline
Abstract/Contents
- Abstract
- A defining step in germ cell development is the exit from mitotic proliferation and initiation of meiosis, which enables the generation of haploid gametes. The switch from mitosis to meiosis must be strictly regulated to maintain proper tissue homeostasis and prevent the formation of germ cell tumors. However, the molecular mechanisms that drive the switch from mitotic proliferation to meiosis and differentiation in metazoans are not well understood. It is also not known whether key regulators of the switch are broadly conserved. Here I show that in the Drosophila male germline, the tumor suppressor proteins Benign gonial cell neoplasm (Bgcn) and Bag-of-marbles (Bam) work together to execute the transition from cell proliferation to differentiation through translational repression. Loss-of-function mutations in either bgcn or bam lead to overproliferation of progenitor cells that fail to enter meiosis and differentiate. Bam and Bgcn directly repress the expression of the target mRNA mei-P26 during the mitotic divisions by binding the mei-P26 3′ UTR. Our studies highlight the important role of translational control mechanisms in making the switch from proliferation to differentiation sharp and accurate in the Drosophila germline. I also identified the mammalian homolog of Drosophila bgcn and found that, strikingly, similar to bgcn mutant flies, mBgcn knockout mice are viable but both male and female sterile. mBgcn expression is upregulated at the onset of meiosis in both male and female germ cells. Consistent with the expression pattern of mBgcn, histological analysis of mBgcn mutant adult testes and fetal ovaries revealed that mBgcn-deficient germ cells fail to enter meiotic prophase and instead attempt an additional mitotic division, and then quickly die. My findings indicate that Bgcn has a highly conserved functional role as a gatekeeper to meiotic entry and terminal differentiation in both flies and mice. In addition, my results raise the exciting possibility that, as in Drosophila males, post-transcriptional control mechanisms may drive the switch from mitosis to meiosis in the mammalian germline.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2015 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Bailey, Alexis Suzanne | |
|---|---|---|
| Associated with | Stanford University, Cancer Biology Program. | |
| Primary advisor | Fuller, Margaret | |
| Thesis advisor | Fuller, Margaret | |
| Thesis advisor | Nusse, Roel, 1950- | |
| Thesis advisor | Oro, Anthony, 1958- | |
| Thesis advisor | Villeneuve, Anne, 1959- | |
| Advisor | Nusse, Roel, 1950- | |
| Advisor | Oro, Anthony, 1958- | |
| Advisor | Villeneuve, Anne, 1959- |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Alexis Suzanne Bailey. |
|---|---|
| Note | Submitted to the Program in Cancer Biology. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2015. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2015 by Alexis Suzanne Bailey
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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