Research Scientist
Ph.D. 1985, University of North Carolina at Chapel Hill
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Neuron-glia interactions in the development of the nervous system
Glial cells, the most numerous cell type in the brain, once were relegated to the status of supporting cells for neurons. Recent research, however, has cast the glia in a new light, revealing them to be involved with neurons in complex interactions that strongly affect the viability, growth, and functioning of the neurons. During development, glial cells have especially important roles in the survival and migration of neurons, guidance of axons, and formation of neuronal branching patterns. But most interestingly, the neurons in turn influence glial cell development, suggesting that a dynamic interaction between the two cell classes is a necessary element in correct development of the nervous system. Because recognition of these neuron-glia interactions is so new, our knowledge of the repertoire of interactions undoubtedly is incomplete and our understanding of the underlying mechanisms is nascent.
To study the role of neuron-glia interactions during development, I use the developing olfactory system of the moth Manduca sexta, an animal whose sensory periphery is easily accessible and manipulable, and whose olfactory pathway develops during metamorphosis. During this period, olfactory receptor neurons send their axons to the antennal (olfactory) lobe. There the axons induce the formation of structures called glomeruli, which appear in virtually all olfactory systems across the animal kingdom. We have found that glial cells have a vital role in the process of glomerulus formation. Although the receptor axons initiate the formation of glomeruli, the newly forming glomeruli must be stabilized by glial cells, which form a glomeruli. When the glial cell population is severely reduced, the mature antennal lobe lacks glomeruli. The involvement of glial cells in the development of the antennal lobe begins even earlier, however, when the receptor axons first approach the antennal lobe. Just outside the lobe, the axons enter a glia-rich domain where they undergo a sorting process that changes their topographic organization to a chemotopic organization, a process that also must be accomplished by vertebrate olfactory axons. In the moth, the axons fail to sort properly in glia-deficient olfactory systems, strongly suggesting that a glia-neuron interaction underlies the process of axon sorting.
In ongoing studies done in collaboration with Leslie Tolbert, we are using a variety of techniques to examine the cellular and molecular bases of the neuron-glia interactions in the sorting zone and in the developing glomeruli. These include cell culture, electrophysiology, immunocytochemistry, electron microscopy, confocal microscopy and live-cell imaging. Given the many similarities between the moth and the vertebrate olfactory systems, we expect that insights gained in studying the moth system will be broadly applicable in understanding the role of neuron-glia interactions in the developing vertebrate system.
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