Glia constitute a large fraction of cells in the vertebrate nervous system and surround neuronal receptive endings to form isolated compartments. Most excitatory synapses in the cerebellum and hippocampus are glia-ensheathed. Likewise, glia surround sensory-neuron receptive endings and neuromuscular junctions. While glial compartments influence sensory responses and synaptic transmission and plasticity, the development and functions of glial compartments are only incompletely understood. Our long-term goals are to establish robust in vivo settings for studying glia-neuron interactions, and to use these settings to fully understand glial compartment development and function. Sensory organs are highly suitable systems in which to study these basic principles. They exhibit simple architecture and are of critical importance to animal and human behavior, as they are the portals through which information is introduced into the nervous system. Sensory organs consist of two cell types: sensory neurons or neuron-like cells and glia or glia-like cells, which are required for neuron function. A major advantage of sensory organs is their remarkable similarity across a wide range of organisms. This allows studies in one system to reveal principles conserved in others. The amphid sensory organ of C. elegans is a prototypical sensory organ and is the most studied sensory organ in C. elegans; however, how its glial compartment is formed has not been investigated. Since we initiated our studies of glial signaling compartments, we have characterized a novel mode of dendrite growth that properly positions glial compartments, have characterized neuronal proteins required for sensory receptive ending structure, revealed a key role for glia in regulating sensory neuron receptive ending shape, demonstrated glial developmental plasticity and uncovered its mechanism, and characterized signaling between sensory neurons and their ensheathing glia to promote glial compartment formation. Here we propose to build on our progress to understand both glial and neuronal mechanisms controlling glial compartment size and shape. We will (1) elucidate the mechanism of action of the LIT-1 NEMO-like kinase in glial compartment size control; (2) study the role of the retromer component SNX-1 in glial compartment morphogenesis; and (3) identify neuronal signals required to localize LIT-1 to the glial compartment surface. Together, these studies should provide insight into the dynamic cell interaction and cell shape changes required to form a glial compartment around sensory neuron receptive endings.
Sensory organs are of critical importance to human behavior, as they are the portals through which information enters the nervous system. Human disorders affecting sensory perception are often due to genetic changes that alter normal organ formation, leading to an inability to taste, smell, experience touch, hear, or see. Our studies aim to provide insight into how these organs form, with specific emphasis on the roles of glial compartments in the functionality of these organs.
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