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The corepressor Atrophin specifies odorant receptor expression in Drosophila
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences. Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
2014 (English)In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 28, no 3, 1355-1364 p.Article in journal (Refereed) Published
Abstract [en]

In both insects and vertebrates, each olfactory sensory neuron (OSN) expresses one odorant receptor (OR) from a large genomic repertoire. How a receptor is specified is a tantalizing question addressing fundamental aspects of cell differentiation. Here, we demonstrate that the corepressor Atrophin (Atro) segregates OR gene expression between OSN classes in Drosophila. We show that the knockdown of Atro result in either loss or gain of a broad set of ORs. Each OR phenotypic group correlated with one of two opposing Notch fates, Notch responding, Nba (N(on)), and nonresponding, Nab (N(off)) OSNs. Our data show that Atro segregates ORs expressed in the Nba OSN classes and helps establish the Nab fate during OSN development. Consistent with a role in recruiting histone deacetylates, immunohistochemistry revealed that Atro regulates global histone 3 acetylation (H3ac) in OSNs and requires Hdac3 to segregate OR gene expression. We further found that Nba OSN classes exhibit variable but higher H3ac levels than the Nab OSNs. Together, these data suggest that Atro determines the level of H3ac, which ensures correct OR gene expression within the Nba OSNs. We propose a mechanism by which a single corepressor can specify a large number of neuron classes.-Alkhori, L., Öst, A., Alenius, M. The corepressor Atrophin specifies odorant receptor expression in Drosophila.

Place, publisher, year, edition, pages
Federation of American Societies for Experimental Biology , 2014. Vol. 28, no 3, 1355-1364 p.
Keyword [en]
HDAC, Notch, epigenetic, neuronal differentiation, olfactory system
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-104702DOI: 10.1096/fj.13-240325ISI: 000335324800027PubMedID: 24334704OAI: oai:DiVA.org:liu-104702DiVA: diva2:698614
Available from: 2014-02-24 Created: 2014-02-24 Last updated: 2017-12-05Bibliographically approved
In thesis
1. Mechanisms of sensory neuron diversification during development and in the adult Drosophila: How to make a difference
Open this publication in new window or tab >>Mechanisms of sensory neuron diversification during development and in the adult Drosophila: How to make a difference
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The nervous system contains a vast number of neurons and displays a great diversity in cell types and classes. Even though this has been known for a long time, the exact mechanism of cell specification is still poorly understood. How does a cell know what type of neuron to which it should be specified? It is important to understand cellular specification, not only for our general understanding of biological processes, but also to allow us to develop treatments for patients with destructive diseases, such as Alzheimer’s, Parkinson, cancer or stroke. To address how neuronal specification and thereby diversification is evolved, we have chosen to study a complex but defined set of neurons, the Drosophila olfactory system. Olfactory sensory neurons (OSNs) detect an enormous variety of small volatile molecules with extremely high specificity and sensitivity. The adult Drosophila olfactory system contains 34 OSN classes each defined by their expression of a specific odorant receptor (OR). In both insects and vertebrates, each OSN expresses only one OR. In mouse there are approximately 1200 and in Drosophila 60 different OR genes. Despite the range of mechanisms known to determine cell identity and that the olfactory system is remarkably conserved across the phyla, it is still unclear how an OSN chooses to express a particular OR from a large genomic repertoire. In this thesis, the specification and diversification of the final steps establishing an OSN identity is addressed. We find seven transcription factors that are continuously required in different combinations for the expression of all ORs. The TFs can in different gene context both activate and repress OR expression, making the regulation more economical and indicating that repression is crucial for correct gene expression. We further identified a repressor complex that is able to segregate OR expression between OSN classes and propose a mechanism on how one single co-repressor can specify a large number of neuron classes.Exploring the OSN we found the developmental Hh signalling pathway is expressed in the postmitotic neuron. We show several fundamental similarities between the canonical Drosophila Hh pathway and the cilia mediated Hh transduction in component function. Further investigation revealed a function of cilia mediated Hh signalling in sensory neuron modulator. The results generated here will create a greater in vivo understanding of how postmitotic processes generate neurons with different fates and contribute to the maintaining of neuron function.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2014. 68 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1390
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-104706 (URN)10.3384/diss.diva-104706 (DOI)978-91-7519-428-8 (ISBN)
Public defence
2014-03-21, Berszeliussalen, Campus US, Linköpings universitet, Linköping, 09:00 (English)
Opponent
Supervisors
Available from: 2014-02-24 Created: 2014-02-24 Last updated: 2016-12-28Bibliographically approved

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Alkhori, LizaÖst, AnitaAlenius, Mattias

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