Genetic Analysis of Dendrite Maintenance in Drosophila Sensory Neurons

University Of California, San Francisco, San Francisco CA

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Abstract

DESCRIPTION (provided by applicant): Dendrite arborization patterns are a hallmark of neuronal type and a critical determinant of neuronal function. Although progress has been made in understanding how dendrites come to occupy their territory, almost nothing is known about how dendrites are maintained after establishment of receptive fields. The long-term objectives of this study are to define mechanisms that regulate dendrite maintenance in different neuronal types. The general approach is to use genetic techniques to identify mutant alleles that cell-autonomously affect dendrite maintenance. Detailed genetic and cell-biological analyses of these alleles and subsequent characterization of the neuronal function of the genes they disrupt should provide a basic understanding of mechanisms regulating dendrite maintenance. The specific aims of this study are to characterize the properties of dendrite maintenance in a specific class of Drosophila sensory neurons in which a genetic pathway for dendrite. maintenance has been identified, investigate the underlying mechanisms that regulate maintenance in this neuronal class, and identify additional modes of dendrite maintenance in this and other types of sensory neurons. Defects in dendrite maintenance should lead to loss of synaptic or sensory inputs, defects in neuronal circuits and likely contribute to a number of disease states. In fact, dendrite defects are the strongest correlate with mental retardation and layer III cortical neurons display a progressive loss of dendrites in Down syndrome. Therefore, understanding the phenomenon of dendrite maintenance and its underlying mechanisms has important implications for disease, particularly neurodegenerative disorders. Relevance Dendrite defects are among the strongest pathalogical correlates of mental retardation, but how dendrite formation is regulated during development and deregulated in disease is poorly understood. After dendrites cover their receptive field, they maintain their coverage with very litlle structural change, and this is likely important for proper function of neuronal circuits. Progressive dendrite defects have been observed in Down Syndrome patients, so a better understanding of dendrite maintenance will likely provide important information for our understaing of Down Syndrome and other neurodegenerative disorders.