The Role of Cilia Motility in Axial Morphogenesis
| dc.contributor.advisor | Grimes, Daniel | |
| dc.contributor.author | Irons, Zoe | |
| dc.date.accessioned | 2024-08-07T21:35:14Z | |
| dc.date.available | 2024-08-07T21:35:14Z | |
| dc.date.issued | 2024-08-07 | |
| dc.description.abstract | The spine is the core of the vertebrate body axis, providing structural support and playing a role in establishing body shape. The linearity of the spine is essential for proper function. Scoliosis, or curvature of the spine, is present in 3-4% of the human population and can cause chronic pain as well as compression of the lungs and heart in severe cases. In this dissertation, I used zebrafish to study the role of cilia motility in morphogenesis of the body axis and the development of scoliosis. Previous work has established cilia motility as essential for zebrafish embryos to uncurl their bodies from around the yolk during the first 24 hours post fertilization. In Chapter I, I found that the protein Daw1 regulates the timely onset of cilia motility, and that embryos are able to remodel their body axes up to 3 days post fertilization. In Chapter II, I investigated factors functioning downstream of cilia motility that control body and spine morphogenesis. The Reissner fiber assembles downstream of cilia motility. Using zebrafish lacking Daw1, I showed that this fiber also assembles in response to a delayed cilia motility cue. The expression of the Urotensin-like peptides, Urp1 and Urp2, is increased as a result of cilia motility in the central canal. By generating mutants lacking both peptides, I showed that these peptides are dispensable for early body morphogenesis, but critical for the maintenance of spinal straightness in adulthood. This work revealed new components of spinal morphology that could be playing roles in human scoliosis. Lastly, in Chapter IV I investigated the mechanism stops further morphogenetic tissue movements once a linear body axis is generated. This occurs in embryos lacking Pkd2, a calcium ion channel known to play a role in flow sensory pathways. Using epistatic tests, I showed that pkd2 acts in a pathway independent of cilia motility and fluid flow to prevent axis over-straightening. Collectively, this dissertation advances our understanding of the role of cilia motility, fluid flow, and downstream factors in body axis straightening and the maintenance of spinal straightness. This work contains both unpublished and published co-authored materials. | en_US |
| dc.identifier.uri | https://hdl.handle.net/1794/29746 | |
| dc.language.iso | en_US | |
| dc.publisher | University of Oregon | |
| dc.rights | All Rights Reserved. | |
| dc.subject | cell signaling | en_US |
| dc.subject | cilia | en_US |
| dc.subject | early development | en_US |
| dc.subject | embryology | en_US |
| dc.subject | scoliosis | en_US |
| dc.subject | zebrafish | en_US |
| dc.title | The Role of Cilia Motility in Axial Morphogenesis | |
| dc.type | Electronic Thesis or Dissertation | |
| thesis.degree.discipline | Department of Biology | |
| thesis.degree.grantor | University of Oregon | |
| thesis.degree.level | doctoral | |
| thesis.degree.name | Ph.D. |
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