Led by principal investigator Michael Fox, Ph.D., the Fox Laboratory is interested in understanding the cellular and molecular mechanisms that drive two aspects of synapse formation—synaptic targeting and synaptic differentiation.
Researchers in the Fox Laboratory focus on the visual system in their efforts to uncover mechanisms that drive the initial targeting of synapses. The scientists are interested in understanding how synapses are formed between retinal ganglion cells (RGCs), the output neurons of the retina, and target neurons within the brain. Despite monumental advances in this field, it remains unclear how different classes of RGCs —of which there are more than 22— target functionally distinct nuclei within the brain. One brain region where class-specific targeting of RGC axons is most evident is the LGN —a thalamic relay nucleus that contains three structurally and functionally distinct subnuclei. Since different classes of RGCs target these subnuclei, the researchers hypothesized that regionalized guidance cues must exist to direct class-specific axonal targeting. Fox and his team have now identified candidate molecules that may act as targeting cues for class-specific retinal targeting and are now testing their necessity in retinogeniculate circuit formation.
Once synaptic partners have correctly targeted each other, both sides of the synapse must exchange developmental relevant signals that transform this immature connection into a functioning synapse (a process called synaptic differentiation). Fox is specifically interested in identifying such trans-synaptic organizing cues in the mammalian brain. Fox is particularly interested in the role of extracellular matrix molecules and growth factors in this process. Previous studies from the Fox Laboratory identified roles for these classes of molecules in coordinating synaptic differentiation at the neuromuscular junction—a large peripheral synapse between motoneurons and muscle fibers. Based upon the bio-activities of these extracellular cues at the neuromuscular junction, the researchers are now asking whether similar cues are necessary and sufficient to induce the formation of brain synapses.