Mechanisms of co-differentiation : the D. melanogaster germ cell cyst as a model for cell-cell interactions in development
Abstract/Contents
- Abstract
- Adult stem cells are required throughout life to replenish differentiated cells lost to normal cell turnover or to injury in many tissues. Regulating the balance between stem cell renewal and differentiation by the microenvironment that surrounds cells in a stem cell lineage is crucial for long-term tissue maintenance and disease prevention. While the adult stem cell field has focused primarily on identifying self-renewal signals for tissue-resident stem cells, in this dissertation I focus on identifying mechanisms by which the niche or microenvironment promotes differentiation down a cell lineage in vivo. In this study, I identified mechanisms of crosstalk between cells in an adult stem cell lineage with cells in their surrounding environment that promote cell survival, stem cell bipotentiality, and proper progression through multiple stages of differentiation. I used the genetic model system of the Drosophila male germ line to determine the molecular mechanisms by which somatic cyst cells promote the transition of germ cells from stem cells, to transit amplifying progenitors, to differentiating germ cells that will undergo meiosis. Germ line stem cells (GSCs) divide asymmetrically to produce daughter cells that will undergo four mitotic transit-amplifying divisions before beginning meiosis and terminal differentiation. Following division of a GSC, the daughter cell displaced away from the hub is encapsulated by two somatic cyst cells, which will influence the entire process of germ cell differentiation into mature sperm. The germ cell-cyst cell "mini organ" is an excellent system to study how two cell types co-differentiate to form a functional unit. I identified molecular signaling events in cyst cells that are required at three stages of germ cell differentiation. 1) Cyst cells repress JNK signaling via activity of the Baz/Par-6/aPKC polarity complex to promote survival of germ cells entering early stages of meiotic prophase. 2) Cyst cells respond to BMP signals in order to dampen the GSC response to BMP self-renewal signals, maintaining germ cells in a bipotential state with the capacity to produce differentiated progeny. 3) Cyst cells must stop dividing, change transcriptional programs, and encapsulate the neighboring germ line for germ cells to cleanly enter the transit amplifying progenitor stage. Together, this work highlights the importance of cell-cell communication throughout the development of the germ cell cyst "mini organ, " which may parallel the interactions that promote co-differentiation of neighboring cell types in development and adult tissues.
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 | 2019; ©2019 |
| Publication date | 2019; 2019 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Brantley, Susanna Elizabeth |
|---|---|
| Degree supervisor | Fuller, Margaret T, 1951- |
| Thesis advisor | Fuller, Margaret T, 1951- |
| Thesis advisor | Nusse, Roel, 1950- |
| Thesis advisor | O'Brien, Lucy Erin, 1970- |
| Degree committee member | Kim, Seung K |
| Degree committee member | Nusse, Roel, 1950- |
| Degree committee member | O'Brien, Lucy Erin, 1970- |
| Associated with | Stanford University, Department of Developmental Biology. |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Susanna E. Brantley. |
|---|---|
| Note | Submitted to the Department of Developmental Biology. |
| Thesis | Thesis Ph.D. Stanford University 2019. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2019 by Susanna Elizabeth Brantley
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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