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Cis-Regulatory Mechanisms for Robust Olfactory Sensory Neuron Class-restricted Odorant Receptor Gene 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.
2015 (English)In: PLOS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 11, no 3, e1005051- p.Article in journal (Refereed) Published
Abstract [en]

Odor perception requires that each olfactory sensory neuron (OSN) class continuously express a single odorant receptor (OR) regardless of changes in the environment. However, little is known about the control of the robust, class-specific OR expression involved. Here, we investigate the cis-regulatory mechanisms and components that generate robust and OSN class-specific OR expression in Drosophila. Our results demonstrate that the spatial restriction of expression to a single OSN class is directed by clusters of transcription-factor DNA binding motifs. Our dissection of motif clusters of differing complexity demonstrates that structural components such as motif overlap and motif order integrate transcription factor combinations and chromatin status to form a spatially restricted pattern. We further demonstrate that changes in metabolism or temperature perturb the function of complex clusters. We show that the cooperative regulation between motifs around and within the cluster generates robust, class-specific OR expression.

Place, publisher, year, edition, pages
Public Library of Science , 2015. Vol. 11, no 3, e1005051- p.
National Category
Clinical Medicine
URN: urn:nbn:se:liu:diva-117811DOI: 10.1371/journal.pgen.1005051ISI: 000352197100039PubMedID: 25760344OAI: diva2:811249

Funding Agencies|Swedish Foundation for Strategic Research [F06-0013]; Swedish Research Council [522-2006-6364 / K2007-66P-20436-01-04]

Available from: 2015-05-11 Created: 2015-05-08 Last updated: 2015-09-02
In thesis
1. Mechanisms of Olfactory sensory neuron class maintenance in Drosophila: It is all about design and equilibrium
Open this publication in new window or tab >>Mechanisms of Olfactory sensory neuron class maintenance in Drosophila: It is all about design and equilibrium
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

How the cellular diversity of our body is generated and maintained is still a great mystery regardless of the wealth of research that has been done on this issue. The greatest complexity is found in the nervous system that contains a vast number of neurons and displays a great diversity in cell types and classes. For example the Drosophila olfactory system is a complex but defined set of neurons with extremely high specificity and sensitivity. The 34 OSN classes are each defined by their expression of a specific odorant receptor (OR). During development each OSN chooses one OR from 60 different OR genes in the genome to express. Furthermore, a cell is subject to immense challenges during its life cycle. Confronting each challenge the cell needs to perform its function and maintain its fate. OSNs continue to express the same OR during their  whole life regardless of fluctuations in the environment.

Although 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 final steps of the specification and diversification for establishing an OSN identity is addressed. We find seven transcription factors that are continuously required in different combinations for the expression of the Drosophila ORs. The TFs can in different background context both activate and repress OR expression, making the regulation more economical. We also imply that repression is crucial for correct OR gene expression. We further show that short DNA sequences from OR gene promoters are sufficient to drive OSN class specific expression. These regions contain clusters of TF binding motifs, which we show to be sensitive to any change in their composition or to changes of the internal or external environment. We demonstrate that the chromatin state is responsible for the clusters response to environmental challenges. We reveal that Su(var)3-9 controls the OSN response to environmental stresses. We address the epigenetic mechanisms that initiate and pertain the single OR expression to a single OSN class. Our results show that OSNs have an epigenetic switch marking the end of development and the transition to mature OSNs. This switch supplies the expression of a single OR gene.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2015. 66 p.
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1458
National Category
Cell and Molecular Biology
urn:nbn:se:liu:diva-120992 (URN)978-91-7519-085-3 (print) (ISBN)
Public defence
2015-09-04, Berszeliussalen, Campus US, Linköping, 09:00 (English)
Available from: 2015-09-02 Created: 2015-09-01 Last updated: 2015-09-02Bibliographically approved

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