Mechanisms of Olfactory sensory neuron class maintenance in Drosophila: It is all about design and equilibrium
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
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
Cell and Molecular Biology
IdentifiersURN: urn:nbn:se:liu:diva-120992DOI: 10.3384/diss.diva-120992ISBN: 978-91-7519-085-3 (print)OAI: oai:DiVA.org:liu-120992DiVA: diva2:850485
2015-09-04, Berszeliussalen, Campus US, Linköping, 09:00 (English)
Hassan, Bassem, Professor
Alenius, Mattias, Dr.Thor, Stefan, ProfessorEngblom, David, Dr.
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