Faculty Member - Division of Biological Sciences University of Missouri-Columbia

Transmission electron micrograph of an axon isolated from the 5th lumbar ventral root of an adult mouse. This image shows the transition from compact myelin (on left) to node of Ranvier. The paranodal loops indicate the end of the compact myelin and the beginning of the node of Ranvier. Within the axon, both neurofilaments and microtubules are visible.

Research description

Specification of axonal diameter is a key component of motor system development and functioning, as axonal diameter is major axonal property that specifies the velocity of electrical signal conduction in the nervous system.

The diameter of myelinated axonal segments (internodes) is increased relative to the diameter of unmyelinated axonal segments (Nodes of Ranvier). Compare the diameter of the left side of the axon in the EM to the diameter on the right side of the image. Formation of compact myelin and axonal accumulation of neurofilaments are both required for axonal diameter specification. However, it is unclear how axons and myelinating cells interact to determine axonal diameter. One proposed mechanism is that myelinating cells signal the axon resulting in alterations to the neurofilament network that support radial growth of the axon.

We generate genetically modified mice to investigate the role of the neurofilament network in establishing axonal diameter, thereby influencing conduction velocity.

We are, also interested in the pathogenesis of neurodegenerative diseases such as Charcot-Marie-Tooth, amyotrophic lateral sclerosis (Lou Gehrig's Disease) and spinal muscular atrophy.

Selected publications

Garcia, ML, Rao, MV, Fujimoto, J, Garcia, VB, Shah, SB, Crum, J, Gotow, T, Uchiyama, Y, Ellisman, M, Calcutt, NA, Cleveland, DW. Phosphorylation of Highly Conserved Neurofilament Medium KSP Repeats Is Not Required for Myelin-Dependent Radial Axonal Growth. J Neurosci; 29, 1277-1284, 2009.

Yamanka, K.*, Boillee, S.*, Roberts, E. A.*, Garcia, M. L., McAlonis-Downes, M., Mikse, O. R., Cleveland, D. W., Goldstein, L. S. B. Mutant SOD1 in cell types other than motor neurons and oligodendrocytes accelerates onset of disease in ALS mice. Proc. Natl. Acad. Sci., 105: 7594-7599, 2008.

Rose, F. F., Meehan, P. W., Coady, T. H., Garcia, V. B., Garcia, M. L., Lorson, C. L. The Wallerian degeneration slow (Wlds) gene does not attenuate disease in a mouse model of spinal muscular atrophy. Biochem. and Biophysical Res. Comm., 375, 119-123, 2008.

Barry, D. M., Millecamps, S., Julien, J. P. and Garcia, M. L. New movements in neurofilament transport, turnover and disease. Experimental Cell Research, 313: 2110-2120, 2007.

Garcia, M. L., Lobsiger, C. S., Shah, S. B., Deerinck, T. J., Crum, J., Young, D., Ward, C. M., Crawford, T. O., Gotow, T., Ellisman, M. H., Calcutt, N. A., and Cleveland, D. W. NF-M is an Essential target for the myelin- derived “outside-in” signaling cascade that mediates radial axonal growth. Journal of Cell Biology, 163: 1011-1020, 2003.