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Genomic Analysis of Drosophila Neuronal Remodeling: A Role for the RNA-Binding Protein Boule as a Negative Regulator of Axon Pruning

Hoopfer, Eric D. and Penton, Andrea and Watts, Ryan J. and Luo, Liqun (2008) Genomic Analysis of Drosophila Neuronal Remodeling: A Role for the RNA-Binding Protein Boule as a Negative Regulator of Axon Pruning. Journal of Neuroscience, 28 (24). pp. 6092-6103. ISSN 0270-6474. PMCID PMC2713105. https://resolver.caltech.edu/CaltechAUTHORS:HOOjns08

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Abstract

Drosophila mushroom body (MB) {gamma} neurons undergo axon pruning during metamorphosis through a process of localized degeneration of specific axon branches. Developmental axon degeneration is initiated by the steroid hormone ecdysone, acting through a nuclear receptor complex composed of USP (ultraspiracle) and EcRB1 (ecdysone receptor B1) to regulate gene expression in MB {gamma} neurons. To identify ecdysone-dependent gene expression changes in MB {gamma} neurons at the onset of axon pruning, we use laser capture microdissection to isolate wild-type and mutant MB neurons in which EcR (ecdysone receptor) activity is genetically blocked, and analyze expression changes by microarray. We identify several molecular pathways that are regulated in MB neurons by ecdysone. The most striking observation is the upregulation of genes involved in the UPS (ubiquitin–proteasome system), which is cell autonomously required for {gamma} neuron pruning. In addition, we characterize the function of Boule, an evolutionarily conserved RNA-binding protein previously implicated in spermatogenesis in flies and vertebrates. boule expression is downregulated by ecdysone in MB neurons at the onset of pruning, and forced expression of Boule in MB {gamma} neurons is sufficient to inhibit axon pruning. This activity is dependent on the RNA-binding domain of Boule and a conserved DAZ (deleted in azoospermia) domain implicated in interactions with other RNA-binding proteins. However, loss of Boule does not result in obvious defects in axon pruning or morphogenesis of MB neurons, suggesting that it acts redundantly with other ecdyonse-regulated genes. We propose a novel function for Boule in the CNS as a negative regulator of developmental axon pruning.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1523/JNEUROSCI.0677-08.2008DOIArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/pmc2713105/PubMed CentralArticle
Additional Information:© 2008 Society for Neuroscience. Received Feb. 14, 2008; revised April 7, 2008; accepted April 28, 2008. This work was supported by a fellowship from the National Science Foundation (E.D.H.), an Epilepsy Program Training Grant (A.P.), and National Institutes of Health Grant R37-NS041044 (L.L.). L.L. is a Howard Hughes Medical Institute investigator. We thank S. Wasserman, M. Fuller, and Exelixis for reagents; H. Su, A. Gontang, and W. Hong for assistance; T. Oro for the use of the Laser Capture Microdissection facility; and P. Vitorino and members of the Luo Laboratory, especially B. Tasic and M. Spletter, for comments and discussion.
Funders:
Funding AgencyGrant Number
NSFUNSPECIFIED
NIHR37-NS041044
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Subject Keywords:axon degeneration; mushroom body; neural development; ecdysone; ecdysone receptor; ubiquitin proteasome system; metamorphosis
Issue or Number:24
PubMed Central ID:PMC2713105
Record Number:CaltechAUTHORS:HOOjns08
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:HOOjns08
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:12592
Collection:CaltechAUTHORS
Deposited By: Archive Administrator
Deposited On:13 Dec 2008 06:02
Last Modified:02 Jul 2020 19:01

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