Molecular basis of specification and connectivity of sensory neurons in the olfactory system of Drosophila melanogaster

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The olfactory system discriminates between a large number of odorants using precisely wired projections from neurons in the periphery to neurons in higher brain centers. The ability to respond to an odor is instrumental in driving important behaviors. Olfactory receptor neurons (ORN) express specific receptors and neurons expressing one receptor class innervate the same substructures called glomeruli in the brain. The olfactory system of the fruitfly Drosophila melanogaster exhibits a highly similar organization to the mammalian olfactory system. Its genetic tractability makes it an ideal model to study how this striking specificity in neuron identity and corresponding wiring is achieved. My future research aims at understanding how ORN specificity and connectivity are coordinated genetically, and at identifying the molecular mechanisms that ultimately allow the construction of a functional neuronal network. It is conceivable that the ochestration of specification and connectivity is provided by ORN class specific molecules such as transcription factors. I am proposing two main approaches to find the critical regulators in this process: (1) previously identified mutants from my postdoctoral work showing neuron specification phenotypes and striking connectivity mutants will be analyzed, and (2) in order to discover the neuron-specific transcription factors and the transmembrane receptors that govern class specific wiring, candidate gene groups will be analyzed using overexpression of inhibitory RNA. In an independent approach directly following up my previous work, the function of the FGF receptor Breathless in one specific ORN class will be characterized.