Characterization of mouse Bmp5 regulatory injury element in zebrafish wound models
Abstract/Contents
- Abstract
- The body plan and tissues of an organism are built during development through a series of repeatable and ordered events. Restoring the body plan or the integrity of a tissue following injury is more complex, since no two injuries are exactly alike. Zebrafish, Danio rerio, are champion tissue regenerators, and I begin this dissertation with a review of regeneration biology, specifically through the lens of zebrafish tail regeneration. One emergent theme is that key signaling molecules that specify patterning are used in both development and following injury. However, little is known about how these molecules are re-activated. I focus on understanding the re-activation of one of a classic group of signaling molecules: Bone Morphogenetic Proteins (BMPs). Previous studies have mapped a large "injury response element" (IRE) in the mouse Bmp5 gene that drives expression in bone fractures and other types of injury. Here I show that the large mouse IRE regulatory region is also activated in both zebrafish tail resection and mechanosensory hair cell injury models. Using the ability to test multiple constructs and image temporal and spatial dynamics following injury responses in fish, I have narrowed the original size of the mouse IRE region by over 100-fold and identified a small 142 bp minimal enhancer that is rapidly induced in both mesenchymal and epithelial tissues after injury. These studies identify a small mouse sequence that responds to evolutionarily conserved local signals in wounded tissues and suggest candidate pathways that contribute to BMP reactivation after injury. Mammals have lost much of their capacity to regenerate; reclaiming some of this ability would be of great significance to human health. I discuss potential therapeutic applications suggested by this work, as well as possible roles for the IRE in human diseases beyond acute injuries. I also discuss the tradeoffs that guide evolutionary modifications to the IRE and injury enhancers generally. Together, this work adds new detail to our understanding of how organisms meet the challenge of growing tissue outside the predictable events of development.
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 | 2021; ©2021 |
| Publication date | 2021; 2021 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Heller, Ian Stuart |
|---|---|
| Degree supervisor | Kingsley, David M. (David Mark) |
| Thesis advisor | Kingsley, David M. (David Mark) |
| Thesis advisor | Fuller, Margaret T, 1951- |
| Thesis advisor | Jarosz, Daniel |
| Thesis advisor | Talbot, William S |
| Degree committee member | Fuller, Margaret T, 1951- |
| Degree committee member | Jarosz, Daniel |
| Degree committee member | Talbot, William S |
| Associated with | Stanford University, Department of Developmental Biology |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Ian Stuart Heller. |
|---|---|
| Note | Submitted to the Department of Developmental Biology. |
| Thesis | Thesis Ph.D. Stanford University 2021. |
| Location | https://purl.stanford.edu/nt131sz0702 |
Access conditions
- Copyright
- © 2021 by Ian Stuart Heller
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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