A Functionally Conserved Gene Regulatory Network Module Governing Olfactory Neuron Diversity.
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2016-01
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Sensory neuron diversity is required for organisms to decipher complex environmental cues. In Drosophila, the olfactory environment is detected by 50 different olfactory receptor neuron (ORN) classes that are clustered in combinations within distinct sensilla subtypes. Each sensilla subtype houses stereotypically clustered 1-4 ORN identities that arise through asymmetric divisions from a single multipotent sensory organ precursor (SOP). How each class of SOPs acquires a unique differentiation potential that accounts for ORN diversity is unknown. Previously, we reported a critical component of SOP diversification program, Rotund (Rn), increases ORN diversity by generating novel developmental trajectories from existing precursors within each independent sensilla type lineages. Here, we show that Rn, along with BarH1/H2 (Bar), Bric-à-brac (Bab), Apterous (Ap) and Dachshund (Dac), constitutes a transcription factor (TF) network that patterns the developing olfactory tissue. This network was previously shown to pattern the segmentation of the leg, which suggests that this network is functionally conserved. In antennal imaginal discs, precursors with diverse ORN differentiation potentials are selected from concentric rings defined by unique combinations of these TFs along the proximodistal axis of the developing antennal disc. The combinatorial code that demarcates each precursor field is set up by cross-regulatory interactions among different factors within the network. Modifications of this network lead to predictable changes in the diversity of sensilla subtypes and ORN pools. In light of our data, we propose a molecular map that defines each unique SOP fate. Our results highlight the importance of the early prepatterning gene regulatory network as a modulator of SOP and terminally differentiated ORN diversity. Finally, our model illustrates how conserved developmental strategies are used to generate neuronal diversity.
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Li, Qingyun, Scott Barish, Sumie Okuwa, Abigail Maciejewski, Alicia T Brandt, Dominik Reinhold, Corbin D Jones, Pelin Cayirlioglu Volkan, et al. (2016). A Functionally Conserved Gene Regulatory Network Module Governing Olfactory Neuron Diversity. PLoS Genet, 12(1). p. e1005780. 10.1371/journal.pgen.1005780 Retrieved from https://hdl.handle.net/10161/13274.
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Pelin Cayirlioglu Volkan
The primary intellectual focus of our lab centers on unraveling the molecular and circuit mechanisms through which social experiences mold the brains and responses of organisms. To investigate these phenomena, we employ the fruit fly nervous system as a model and take an interdisciplinary approach that integrates genetic, behavioral, circuit-mapping, and systems-level molecular tools. Recent advancements in neurogenetics and neuro-visualization techniques in Drosophila melanogaster, a model system with a rich history in behavioral and neurogenetic research, provide us with unique and unprecedented advantages for exploring these questions. Within the realm of fruit flies, several noteworthy observations emerge: 1) Social isolation exerts significant effects on the Drosophila brain and behaviors, 2) well-established connections exist between genes, neural circuits, and stereotyped social behaviors, 3) the utilization of gene editing and neuronal circuit mapping methods is unparalleled, and 4) these resources are further enriched by existing and upcoming connectome data. Leveraging this comprehensive toolset, our overarching objective is to identify genes regulated by social isolation, determine their expression and function in individual neurons and circuits in the brain, and ascertain how variations in these processes influence both brain function and behavioral responses to isolation.
Questions we are interested in:
1- How does social experience and pheromone circuit activity modulate gene expression in the nervous system?
2- How does social experience and pheromone circuit activity modulate circuit structure and function?
3- How does social experience and pheromone circuit activity modulate behaviors like locomotion, feeding, courtship and aggression?
4- How does social experience and pheromone circuit activity modulate physiology like metabolism, circulatory system and immunity?
5- What makes individuals more sensitive or resilient to the effects of social experience?
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