liu.seSearch for publications in DiVA
Change search
ReferencesLink to record
Permanent link

Direct link
Mechanisms of Olfactory sensory neuron class maintenance in Drosophila: It is all about design and equilibrium
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
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.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1458
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:liu:diva-120992ISBN: 978-91-7519-085-3 (print)OAI: oai:DiVA.org:liu-120992DiVA: diva2:850485
Public defence
2015-09-04, Berszeliussalen, Campus US, Linköping, 09:00 (English)
Opponent
Supervisors
Available from: 2015-09-02 Created: 2015-09-01 Last updated: 2015-09-02Bibliographically approved
List of papers
1. Combinatorial Activation and Repression by Seven Transcription Factors Specify Drosophila Odorant Receptor Expression
Open this publication in new window or tab >>Combinatorial Activation and Repression by Seven Transcription Factors Specify Drosophila Odorant Receptor Expression
Show others...
2012 (English)In: PLoS biology, ISSN 1544-9173, E-ISSN 1545-7885, Vol. 10, no 3, e1001280- p.Article in journal (Refereed) Published
Abstract [en]

The mechanism that specifies olfactory sensory neurons to express only one odorant receptor (OR) from a large repertoire is critical for odor discrimination but poorly understood. Here, we describe the first comprehensive analysis of OR expression regulation in Drosophila. A systematic, RNAi-mediated knock down of most of the predicted transcription factors identified an essential function of acj6, E93, Fer1, onecut, sim, xbp1, and zf30c in the regulation of more than 30 ORs. These regulatory factors are differentially expressed in antennal sensory neuron classes and specifically required for the adult expression of ORs. A systematic analysis reveals not only that combinations of these seven factors are necessary for receptor gene expression but also a prominent role for transcriptional repression in preventing ectopic receptor expression. Such regulation is supported by bioinformatics and OR promoter analyses, which uncovered a common promoter structure with distal repressive and proximal activating regions. Thus, our data provide insight into how combinatorial activation and repression can allow a small number of transcription factors to specify a large repertoire of neuron classes in the olfactory system.

Place, publisher, year, edition, pages
Public Library of Science, 2012
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-76960 (URN)10.1371/journal.pbio.1001280 (DOI)000302239700004 ()
Note
Funding Agencies|Marie Curie Actions (European Commission)||Swedish Research Council||Swedish Strategic Research Foundation||Boehringer Ingelheim GmbH||DFG||Schram-Foundation||Available from: 2012-04-27 Created: 2012-04-27 Last updated: 2015-09-02
2. Cis-Regulatory Mechanisms for Robust Olfactory Sensory Neuron Class-restricted Odorant Receptor Gene Expression in Drosophila
Open this publication in new window or tab >>Cis-Regulatory Mechanisms for Robust Olfactory Sensory Neuron Class-restricted Odorant Receptor Gene Expression in Drosophila
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
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-117811 (URN)10.1371/journal.pgen.1005051 (DOI)000352197100039 ()25760344 (PubMedID)
Note

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
3. Drosophila olfactory sensory neurons have two phases of gene expression regulation
Open this publication in new window or tab >>Drosophila olfactory sensory neurons have two phases of gene expression regulation
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Here, we investigate the gene regulatory mechanisms that buffer environmental challenges and are required for Drosophila OSNs to maintain their fate. Each OSN expresses one odorant receptor (OR) gene from a large OR gene repertoire and the expression is maintained throughout the life of the neuron. We demonstrate that OSNs transit from a permissive gene regulatory state at the end of development to a robust continuous regulatory state in mature OSNs that secure the expression of a single OR gene. We provide evidence that the switch is associated to a change in the H3K9 methylation state. We show that the H3K9 demetylase su(var)3-3 is required for the permissive phase and the robust phase require the H3K9 methylase, su(var) 3-9. We further show that H3K9 methylation status has a role in the regulation of gene expression during the environmental challenges. Thus, our data demonstrate that OSNs go through two separate phases that compensate the environmental fluctuations differently.

National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-120991 (URN)
Available from: 2015-09-01 Created: 2015-09-01 Last updated: 2015-09-02Bibliographically approved

Open Access in DiVA

omslag(6207 kB)25 downloads
File information
File name COVER01.pdfFile size 6207 kBChecksum SHA-512
a09dfaa0db8e973ec03f70ac40db8720fd4ce8e58b7540e8c82f1b6afe3b88e461ed1d90bbf7ce51eb5dbd1aa750afc10f248286116fe8b50c62f6f9858727a3
Type coverMimetype application/pdf

Search in DiVA

By author/editor
Jafari, Shadi
By organisation
Division of Cell BiologyFaculty of Medicine and Health Sciences
Cell and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Total: 574 hits
ReferencesLink to record
Permanent link

Direct link