Dendrites have diverse morphologies that are important for the neuron to properly process synaptic information. The spatial patterning of a neuron?s dendritic arbor with respect to that of its neighbor is particularly relevant in sensory systems where stimulus detection must be efficient for downstream processing. In a phenomenon called dendritic tiling, neurons from a functional class that encode the same stimuli segregate into distinct mosaic patterns so that their dendrites rarely overlap with one another. Such dendritic tiling allows for spatial acuity by the nonredundant coverage of a receptive field.
Specific Aim 1 will test the hypothesis that activity-dependent mechanisms result in tiling of dendrites in the nematode C. elegans using live imaging of neighboring neurons labeled with distinct fluorescent reporters.
In Specific Aim 2, genetic approaches will be utilized to assess the impact of extracellular ligands on downstream actin regulation necessary for tiling. This proposal will yield insights into the cell biology of how dendrites from adjacent neurons avoid one another, as well as the novel mechanisms that regulate dynamic growth and retraction of dendrites during neural circuit assembly. Because dendritic pathologies have been observed in human patients with intellectual disorders, the proposed studies will also have applications that can contribute to potential therapies and preventative measures of neurological diseases.
Peripheral neuropathies in humans partially result from the aberrant connectivity between sensorimotor neurons and skin. A better understanding of the cell biological mechanisms that orchestrate the segregation of sensory neuron dendrites is crucial for the discovery of fundamental knowledge about how dendrites define their cellular territories and, perhaps in the long-term, for the discovery of targeted approaches for treatment of peripheral nerve disorders. The following proposal will document the process of dendritic tiling as it occurs in vivo, test the activity-dependent regulation of tiling, and determine the necessity of extracellular ligands to regulate the actin cytoskeleton.
