Files and links (1)
PDFOpen Access (License Unspecified), Open Access
Dissertation
The Drosophila chromodomain protein Kismet epigenetically regulates ecdysone steroid hormone receptor expression to affect axon pruning in vivo
Doctor of Philosophy (Ph.D.), Drexel University
2019
DOI:
https://doi.org/10.17918/frjv-b439
Abstract
Axon pruning is a critical part of proper synapse elimination which is necessary for sculpting precise neural circuits in all animals, from invertebrates to vertebrates alike. Although this vital process has been described in the literature for decades, relatively little is known about the molecular and cellular mechanisms that govern axon pruning in vivo. Here, we show that the epigenetic chromodomain protein Kismet is required for developmental axon pruning in the mushroom bodies of the central brain of Drosophila melanogaster. Kismet binds to cis-regulatory elements of the steroid hormone receptor ecdysone receptor (ecr) gene in the central nervous system and is required for activating expression of EcR-B1. At the ecr locus, Kismet promotes the histone modifications H3K36 di- and tri-methylation and H4K16 acetylation which are associated with actively transcribed chromatin. We show that transgenic EcR-B1 can rescue the axon pruning and memory defects associated with loss of Kismet, and excitingly that pharmacological inhibition of histone deacetylases using SAHA can also rescue these phenotypes in vivo. EcR protein abundance is the cell-autonomous, rate-limiting step required to initiate axon pruning in Drosophila, and our novel data suggests that this step is under the epigenetic control of Kismet.
Metrics
30 File views/ downloads
11 Record Views
Details
- Title
- The Drosophila chromodomain protein Kismet epigenetically regulates ecdysone steroid hormone receptor expression to affect axon pruning in vivo
- Creators
- Nina Krassimirova Latcheva - DU
- Contributors
- Daniel Marenda (Advisor) - Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- x, 126 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; College of Medicine; Drexel University
- Other Identifier
- 9361; 991014632061404721