Kaan Mika’s research while affiliated with University of Lausanne and other places

The singular expression of insect olfactory receptors in specific populations of olfactory sensory neurons is fundamental to the encoding of odors in patterns of neuronal activity in the brain. How a receptor gene is selected, from among a large repertoire in the genome, to be expressed in a particular neuron is an outstanding question. Focusing on Drosophila melanogaster, where most investigations have been performed, but incorporating recent insights from other insect species, we review the multilevel regulatory mechanisms of olfactory receptor expression. We discuss how cis-regulatory elements, trans-acting factors, chromatin modifications, and feedback pathways collaborate to activate and maintain expression of the chosen receptor (and to suppress others), highlighting similarities and differences with the mechanisms underlying singular receptor expression in mammals. We also consider the plasticity of receptor regulation in response to environmental cues and internal state during the lifetime of an individual, as well as the evolution of novel expression patterns over longer timescales. Finally, we describe the mechanisms and potential significance of examples of receptor co-expression.

In olfactory systems across phyla, most sensory neurons express a single olfactory receptor gene selected from a large genomic repertoire. We describe previously unknown receptor gene-dependent mechanisms that ensure singular expression of receptors encoded by a tandem gene array [Ionotropic receptor 75c (Ir75c), Ir75b, and Ir75a, organized 5' to 3'] in Drosophila melanogaster Transcription from upstream genes in the cluster runs through the coding region of downstream loci and inhibits their expression in cis, most likely via transcriptional interference. Moreover, Ir75c blocks accumulation of other receptor proteins in trans through a protein-dependent, posttranscriptional mechanism. These repression mechanisms operate in endogenous neurons, in conjunction with cell type-specific gene regulatory networks, to ensure unique receptor expression. Our data provide evidence for inter-olfactory receptor regulation in invertebrates and highlight unprecedented, but potentially widespread, mechanisms for ensuring exclusive expression of chemosensory receptors, and other protein families, encoded by tandemly arranged genes.

In olfactory systems across phyla, most sensory neurons transcribe a single olfactory receptor gene selected from a large genomic repertoire. We describe novel receptor gene-dependent mechanisms that ensure singular expression of receptors encoded by a tandem gene array in Drosophila . Transcription from upstream genes in the cluster runs through the coding region of downstream loci to inhibit their expression in cis , via transcriptional interference. Moreover, one receptor blocks expression of other receptor proteins in trans through a post-transcriptional mechanism. These repression mechanisms operate in endogenous neurons to ensure their unique expression. Our data provide evidence for inter-olfactory receptor regulation in invertebrates, and highlight unprecedented, but potentially widespread, mechanisms for ensuring exclusive expression of chemosensory receptors, and other protein families, encoded by tandemly-arranged genes.

Determining the molecular properties of neurons is essential to understand their development, function and evolution. Using Targeted DamID (TaDa), we characterize RNA polymerase II occupancy and chromatin accessibility in selected Ionotropicreceptor (Ir)-expressing olfactory sensory neurons in Drosophila. Although individual populations represent a minute fraction of cells, TaDa is sufficiently sensitive and specific to identify the expected receptor genes. Unique Ir expression is not consistently associated with differences in chromatin accessibility, but rather to distinct transcription factor profiles. Genes that are heterogeneously-expressed across populations are enriched for neurodevelopmental factors, and we identify functions for the POU-domain protein Pdm3 as a genetic switch of Ir neuron fate, and the atypical cadherin Flamingo in segregation of neurons into discrete glomeruli. Together this study reveals the effectiveness of TaDa in profiling rare neural populations, identifies new roles for a transcription factor and a neuronal guidance molecule, and provides valuable datasets for future exploration.

Determining the molecular properties of neurons is essential to understand their development, function and evolution. We used Targeted DamID (TaDa) to characterize RNA polymerase II occupancy and chromatin accessibility in selected Ionotropic Receptor (IR)-expressing sensory neurons in the Drosophila antenna. Although individual populations represent a minute fraction of cells, TaDa is sufficiently sensitive and specific to identify the expected receptor genes. Unique Ir expression is not linked to substantial differences in chromatin accessibility, but rather to distinct transcription factor profiles. Heterogeneously-expressed genes across populations are enriched for neurodevelopmental factors, and we identify functions for the POU-domain protein Pdm3 as a genetic switch of Ir neuron fate, and the atypical cadherin Flamingo in segregation of neurons into discrete glomeruli. Together this study reveals the effectiveness of TaDa in profiling rare neural populations, identifies new roles for a transcription factor and a neuronal guidance molecule, and provides valuable datasets for future exploration.