Molekulare Mechanismen der Spezifizierung und Konnektivität von sensorischen Neuronen im olfaktorischen System von Drosophila melanogaster
Zusammenfassung der Projektergebnisse
Hundreds of times a day animals encounter different sensory stimuli that need to be processed dependent on their internal state and environmental context to trigger appropriate actions and behaviors. Moreover, these behaviors depend strongly on the animal species and its biological niche. Therefore, neural circuits have hard-wired species specific components that nevertheless allow for the integration of their internal state and the current situation they are facing. In light of this, my research tries to answer several important questions: (i) What are the neural circuits underpinning species specific innate behavior, (ii) how do they form, and (iii) how are current state and environmental context integrated into innate behavior on the neural circuit level? To this aim, my laboratory uses the Drosophila model system in combination with state of the art techniques in neurobiology. With the support of Emmy Noether funding, we have focused on the formation of the sensory, in particular olfactory circuits in the fly. Building on a large histological screen I have carried out as a postdoc, we have identified several molecular players involved in the formation of olfactory circuits in the fly. First, because mosquitoes and flies show opposite innate behavior to the ubiquitous gas CO2, we investigated the development of the CO2 sensory system. We identified a small molecular network consisting of a microRNA, mir-279, the transcription factor Prospero, and two downstream transcription factors that together prevent the formation of a CO2 sensory system that is similar to mosquitoes in the fly. Currently, we are investigating whether these molecules could help to change the sensory perception of CO2 by mosquitoes from positive to negative as it is the case in flies. Next, we found that the highly conserved protein Psidin (human NatB) is required during two important processes in the development of the olfactory system. Psidin’s N-acetyltransferase activity is required to produce the right number of olfactory neurons, while Psidin’s interaction with the actin cytoskeleton ensures their proper connectivity within the brain. Interestingly, we implicated a phosphorylationdependent mechanism that controls the relative use of these two mechanisms using a phosphorylation site that is also conserved in humans. Finally, I invested funds of the grant to setup methods and techniques in the lab that allowed us to start tackling the important problem of how olfactory information is processed in the fly brain. Using these methods, we demonstrated that the mushroom body assumed to be exclusively required in olfactory learning and memory is required for hunger state-dependent processing of CO2. Thus, the mushroom body not only integrates olfactory information with other information for learning purposes, but also to modulate instant odor guided behavior. Our work on the CO2 sensory system gained some media attention in several newspapers or online portals. Taken together, we were able to gain some answers to the questions posed above. First, we advanced our understanding of the neural processing of olfactory cues and how context is integrated and modulates innate behavior. And second, our work identified some new players in the development of these circuits, some of which have the potential to be involved in the divergence of species specific behavior. My research continues to try to deepen our understanding of these important problems in neuroscience with hopes of contributing to closing the gap between genes and behavior.
Projektbezogene Publikationen (Auswahl)
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(2011) A New Prospero and microRNA-279 Pathway Restricts CO2 Receptor Neuron Formation. Journal of Neuroscience 31(44): 15660-73
Hartl, M., Loschek, L.F., Stephan, D., Siju, K.P., Knappmeyer, C., Grunwald Kadow, I.C.
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(2012) Drosophila Psidin regulates olfactory neuron number and axon targeting through two distinct molecular mechanisms. Journal of Neuroscience 32(46):16080-94
Stephan, D., Sanchez-Soriano, N., Loschek, L.F., Gerhards, R., Gutmann, S., Storchova, Z., Prokop, A. and Grunwald Kadow, I.C.
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(2013) Retinotopic map formation in Drosophila requires Gogo receptor during three developmental steps. PLOS one Jun 24;8(6):e66868
Hein, I., Suzuki, T. and Grunwald Kadow, I.C.
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(2013). New roles for ‘old’ microRNAs in nervous system function and disease. Front Mol Neurosci
Hartl M., Grunwald-Kadow I.C.
