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Hh signalling regulates odorant receptor cilia localization 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. Linköping University, Faculty of Health Sciences.
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.
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2014 (English)Manuscript (preprint) (Other academic)
Abstract [en]

Hedgehog (Hh) signaling is a key regulatory pathway during development. Here, we show that in adult OSNs the Hh pathway regulate 􀁒dorant receptor transport to cilia and put forward a novel non-developmental function of the pathway as a neuromodulator. We demonstrate that the level of Hh signal modulate the OSNs response to odors. We show that knock down of Hh and Smoothened (Smo), a transmembrane protein that transduce the signal, are required for receptor transport. We further show that the coreceptor, Orco, has an Hh independent transport path and that knock down of Smo segregate OR and Orco to different vesicular compartments. Last, we show that the odor response to the second receptor type in Drosophila olfaction, the ionotropic receptors (IRs), also require Hh signalling. Thus, Hh signalling is a general regulator of the odorant response that fulfils the criteria of being a potential player in Drosophila odorant adaptation.

Place, publisher, year, edition, pages
2014.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-104705OAI: oai:DiVA.org:liu-104705DiVA: diva2:698619
Available from: 2014-02-24 Created: 2014-02-24 Last updated: 2014-02-24Bibliographically 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)
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Supervisors
Available from: 2014-02-24 Created: 2014-02-24 Last updated: 2016-12-28Bibliographically approved

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Alkhori, LizaSanchez, Gonzalo M.Schultz, Sebastian W.Kuzhandaivel, AnujaianthiGranseth, BjörnAlenius, Mattias

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Alkhori, LizaSanchez, Gonzalo M.Schultz, Sebastian W.Kuzhandaivel, AnujaianthiGranseth, BjörnAlenius, Mattias
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Division of Cell BiologyFaculty of Health SciencesDepartment of Clinical and Experimental MedicineThe Institute of Technology
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