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Dimitrova, Svetla (2007): Physiological Roles of Robo Receptor during dendrite development of the multidendritic arborization neurons of the Drosophila peripheral nervous system. Dissertation, LMU München: Fakultät für Biologie



Elaboration of a dendritic arbor and the extension of an axon define the neuronal shape and are the key morphological features defining neuronal maturation. How the process is molecularly regulated is only poorly understood. In this study we used the dorsal multidendritic arborization (md-da) neurons of the Drosophila embryonic Peripheral Nervous System(PNS) to address the question about the Roundabout (Robo) receptor protein function during dendrite field development. We identified Robo as one of the proteins involved in regulating the balance between dendritic branch elongation and new branch formation during dendritic arbor specification of the morphologically most complex, filling-in Class IV neuron of Drosophila PNS. To dissect the role of the Robo proteins during dendritogenesis, we performed detailed developmental analyses of dendrite field formation of md-da neurons and compared how dendrite morphogenesis differs in animals lacking Robo function or having too much of the protein in their sensory neurons. We observed that changing the function of Robo protein results in defects in the number and elongation of high order dendritic branches. With the help of cell-class specific genetic markers we also observed that Robo acts cell- class specifically and is required during dendrite field development of the morphologically most complex class of md-da neurons, Class IV. Based on MARCM (mosaic analyses with a repressible cell marker) rescue and expression pattern experiments we suggest that this function of Robo is cell-autonomous. By doing time-lapse analyses we assessed the mechanistic role of overexpressing Robo during dendrite field development. We could verify that this protein limits the elongation and new branch formation of fine dendritic processes of the Dorsophila Class IV neurons. We performed expression pattern analyses, ectopic expression experiments and MARCM experiments for slit and suggest that muscles and neurons themselves are possible sources for the ligand. There are few molecules known to mediate the activation of Robo via Slit in the growth cone of an axon. Among these are Dock, a SH2-SH3 adaptor protein and Ena, a member of the VASP family of proteins. Loss-of-function analyses for these two proteins suggest that Ena is acting downstream of Robo during the regulation of dendrite field development of md-da neurons. Finally we propose a model in which Robo responsiveness to Slit is down regulated via Robo2 during axon patterning of dorsal md- da neurons.