Deconstructing Collective Cell Death in a Genetic Model
| dc.contributor.advisor | Rothenfluh, Adrian | en |
| dc.contributor.committeeMember | Abrams, John M. | en |
| dc.contributor.committeeMember | Kraus, W. Lee | en |
| dc.contributor.committeeMember | Krämer, Helmut | en |
| dc.creator | Garcia Hughes, Gianella | en |
| dc.creator.orcid | 0000-0002-4729-4443 | |
| dc.date.accessioned | 2017-09-05T14:53:55Z | |
| dc.date.available | 2017-09-05T14:53:55Z | |
| dc.date.created | 2015-08 | |
| dc.date.issued | 2015-07-27 | |
| dc.date.submitted | August 2015 | |
| dc.date.updated | 2017-09-05T14:45:36Z | |
| dc.description.abstract | Elimination of cells and tissues by apoptosis is a highly conserved process. In Drosophila, the entire wing epithelium is completely removed shortly after eclosion. The cells that make up this epithelium are collectively eliminated through a highly synchronized form of apoptotic cell death, involving canonical apoptosome genes. Here I present evidence that transcription of the IAP antagonist, head involution defective (hid), is acutely induced in wing epithelial cells prior to this process. hid mRNAs accumulate to levels that exceed a component of the ribosome and likewise, Hid protein becomes highly abundant in these same cells. hid function is required for collective cell death, since loss of function mutants show persisting wing epithelial cells and, furthermore, silencing of the hormone bursicon in the CNS produced collective cell death defective phenotypes manifested in the wing epithelium. Taken together, these observations suggest that acute induction of Hid primes wing epithelial cells for collective cell death and that Bursicon is a strong candidate to trigger this process, possibly by activating the abundant pool of Hid already present. This model of collective cell death in the wing is predictable, easy to observe, and experimentally tractable. Previous studies have shown that mutants in the canonical apoptotic pathways share a late-onset blemishing and persisting cells phenotypes and here I present data of two other possible cell death gene candidates. First, I show that a compound deletion, 33B(del), which removes vps33B and part of fur1, generates late-onset blemishes and persisting cells in the wing blade. These phenotypes cannot be rescued by a vps33B genomic rescue, and the possibility exists that the phenotypes are due to fur1. Finally, I show that silencing of CTCF, a protein involved in chromosomal looping and 3D genomic organization, also generates late-onset blemishes and persisting cells in the wing blade. These results, together with the binding sites annotation in the Reaper region, suggest that CTCF might be coordinating the expression of the IAP antagonists, hid in particular, by chromosomal looping. Taken together, these studies contribute to the characterization of collective cell death in Drosophila. | en |
| dc.format.mimetype | application/pdf | en |
| dc.identifier.oclc | 1002857161 | |
| dc.identifier.uri | https://hdl.handle.net/2152.5/4223 | |
| dc.language.iso | en | en |
| dc.subject | Apoptosis | en |
| dc.subject | Drosophila melanogaster | en |
| dc.subject | Drosophila Proteins | en |
| dc.subject | Neuropeptides | en |
| dc.subject | Wings, Animal | en |
| dc.title | Deconstructing Collective Cell Death in a Genetic Model | en |
| dc.type | Thesis | en |
| dc.type.material | text | en |
| thesis.degree.department | Graduate School of Biomedical Sciences | en |
| thesis.degree.discipline | Genetics and Development | en |
| thesis.degree.grantor | UT Southwestern Medical Center | en |
| thesis.degree.level | Doctoral | en |
| thesis.degree.name | Doctor of Philosophy | en |