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, very little is known about how neurons maintain dendritic coverage of their receptive field. Since dendrite defects are the strongest correlate with mental retardation, understanding the phenomenon of dendrite maintenance and its underlying mechanisms has important implications for disease, particularly neurodegenerative disorders. Nevertheless, technical limitations have made dendrite maintenance a largely intractable phenomenon. The long-term objectives ofthis study are to define mechanisms that regulate dendrite maintenance in different neuronal types. The general approach is to use genetic screening and microarray-based gene expression profiling to identify genes that cell-autonomously regulate dendrite maintenance. Detailed genetic and cellbiological analyses ofthe neuronal function of these genes should provide a basic understanding of mechanisms regulating dendrite maintenance.
The specific aims ofthis study are (1) to identify genes that are rquired for dendrite maintenance and mutationally define different modes of dendrite maintenance in Drosophila sensory neurons, (2] to characterize the molecular and cell-biological changes that occur as a neuron transitions from establishing to maintaining receptive field coverage, and (3) to gain insight into how establishment and maintenance of receptive field coverage are coordinated in a given neuron.
Dendrite defects are among ttie strongest pathalogical correlates of mental retardation, and maintenance of dendrite coverage is likely disrupted in some of ttiese diseases. For example, Down Syndrome patients display progressive defects in maintenance of dendritic arbors of cortical neurons. Ttius, understanding how neurons maintain receptive field coverage will contribute to our understanding of mental retardation.
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