Michael Fox, PhD
Associate Professor, VTC Research Institute
Associate Professor, Biological Sciences, College of Science at Virginia Tech
Research Program Summary
Synapses are specialized sites that allow information to be passed between neurons. Their importance is highlighted by the fact that even minor synaptic abnormalities, caused by disease or neurotrauma, result in devastating neurological conditions. Understanding how CNS synapses are formed is therefore essential to our understanding of neurological disorders. My lab is interested in understanding the cellular and molecular mechanisms that drive two aspects of synapse formation—synaptic targeting and synaptic differentiation.
Our efforts to uncover mechanisms that drive the initial targeting of synapses focus on the visual system. We 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 still 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, we hypothesized that regionalized guidance cues must exist to direct class-specific axonal targeting. We 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). My lab is specifically interested in identifying such trans-synaptic organizing cues in the mammalian brain. We are particularly interested in the role of extracellular matrix molecules and growth factors in this process. Our previous studies 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, we are now asking whether similar cues are necessary and sufficient to induce the formation of brain synapses.
Education and Training
- Harvard University: Postdoctoral fellowship
- Virginia Commonwealth University: Ph.D., Anatomy
- College of William and Mary: B.S., Chemistry
- Singh R, Su J, Brooks JM, Terauchi A, Umemori H, Fox MA. (2012). Fibroblast growth factor 22 contributes to the development of retinal nerve terminals in the dorsal lateral geniculate nucleus. Frontiers in Molecular Neuroscience, 4:61.
- Su J, Stenbjorn RS, Gorse K, Su K, Hauser KF, Ricard-Blum S, Pihlajaniemi T, Fox MA. (2012). Target-derived matricryptins organize cerebellar synapse formation through α3β1 integrins. Cell Reports, 2(2):223-30.
- Valdez G, Tapia JC, Lichtman JW, Fox MA, Sanes JR. (2012). Shared resistance to aging and ALS in neuromuscular junctions of specific muscles. PLoS ONE, 7(4):e34640.
- Fox MA, Tapia JC, Kasthuri N, Lichtman JW. (2011). Delayed synapse elimination in mouse levator palpebrae superioris muscle. J Comp Neurol, 519(15):2907-2921.
- Su J, Haner CV, Imbery TE, Brooks JM, Morhardt DR, Gorse K, Guido W, Fox MA. (2011). Reelin is required for class-specific retinogeniculate targeting. J Neurosci, 31(2):575-86.
- Fox MA, Guido W. (2011). Shedding light on class-specific wiring: Development of intrinsically photosensitive retinal ganglion cell circuitry. Mol Neurobiol, 44(3):321-9.
- Latvanlehto A, Fox MA, Sormunen R, Tu H, Oikarainen T, Koski A, Naumenko N, Shakirzyanova A, Kallio M, Ilves M, Giniatullin R, Sanes JR, Pihlajaniemi T. (2010). Muscle-derived collagen XIII regulates maturation of the Skeletal Neuromuscular Junction. J Neurosci, 30(37):12230-41.
- Su J, Gorse K, Ramirez F, Fox MA. (2010). Collagen XIX is expressed by interneurons and contributes to hippocampal synapse formation. J Comp Neurol, 518(2):229-53.
- Fox MA, Sanes JR, Borza DB, Eswarakumar VP, Fässler R, Hudson BG, John SW, Ninomiya Y, Pedchenko V, Pfaff SL, Rheault MN, Sado Y, Segal Y, Werle MJ, Umemori H. (2007). Distinct target-derived signals organize formation, maturation, and maintenance of motor nerve terminals. Cell, 129(1):179-93.