Thomas Gould, Ph.D.

Project 3: The Roles of Glia and Neural Activity in the Development of Neuromuscular Synapses

Dr. Gould

Glial cells play a variety of important roles in the development and function of the nervous system. Recent studies have shown that glia regulate the formation, maturation and function of synapses. For example, in embryonic mice lacking Schwann cells, a subtype of glia found in the peripheral nervous system, synapses form but cannot be maintained. This leads to withdrawal of motor and sensory axons from their targets and subsequent cell death.

While the conventional view holds that positive or trophic factors are released from Schwann cells and act to maintain the synapse, our recent work identified a different pathway. We found that Schwann cells release factors that oppose the synapse-destabilizing factors from muscle. These negative factors are induced by neural activity because elimination of activity suppresses synapse destabilization, axon withdrawal and cell death. One of these negative factors is the clotting factor thrombin, which is expressed by muscle, induced by activity and blocked by Schwann cell-derived antithrombins.

These studies suggest that activity-dependent pathways are regulated by interactions between glial cells and developing neurons. Therefore, using mice expressing genetically encoded calcium sensor molecules, we propose to measure early synaptic activity directly in mouse embryos with or without Schwann cells. We suspect that this line of inquiry will be useful to examine early neuromuscular activity in mutant mouse models of Charcot-Marie Tooth disease, which exhibit profound hypomyelination of peripheral nerves during early postnatal development. It will also be useful for examining congenital motor neuron disease, in which neuromuscular synaptic maintenance is also severely compromised.


Project 3 Team

Thomas GouldThomas Gould, Ph.D.

Project 3 Leader

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Dean BurkinDean Burkin, Ph.D.

Project 3 Mentor

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James KenyonJames Kenyon, Ph.D.

Project 3 Mentor

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