SCoBIRC FACULTY

Diane M. Snow, Ph.D.

Professor, Department of Anatomy & Neurobiology

Case Western Reserve University, Cleveland, OH (1990)
Postdoctoral training at The University of Minnesota, Minneapolis, MN
Associate Professor of Anatomy and Neurobiology

Research Interests

Neuronal Growth Cone Guidance and Extracellular Matrix Molecules
The functional organization of the adult nervous system depends upon the connections formed during development, when axons extend from neuronal cell bodies and navigate along specific pathways toward their targets. The direction of axonal extension is accomplished by the growth cone - the motile structure at the distal tip of the elongating Inhibition of neurite outgrowthaxon. Growth cones detect and respond to positive and negative signals, or guidance cues, in the nervous system milieu, e.g., cell surface and extracellular matrix (ECM) molecules. Dr. Snow's research focuses on a class of ECM molecule, the proteoglycans, specifically the chondroitin sulfate proteoglycans (CSPGs), and their effect on migrating growth cones. CSPGs are located in regions where axons do not grow in vivo, e.g. the roof plate, and act as inhibitors of neurite outgrowth in vitro. Further, CSPGs are upregulated following nervous system injury where they may prevent nerve regeneration. An understanding of the role of PGs will offer new insights into nervous system development, causes for a lack of recovery of function following injury, and potential targets for strategies and therapies for the treatment of nervous system injury.

In an effort to understand the regulatory mechanism(s) governing growth cone migration by CSPGs, both during development and following injury, the experimental goals are to: 1) determine whether PGs inhibit neurite outgrowth by blocking the influence of growth- promoting ECM molecules, such as laminin; 2) determine the role of second messengers and signaling cascades in the CSPG-induced inhibitory response; 3) determine the role of theneuronal cytoskeleton in growth cone turning in response to contact with inhibitory molecules, and 4) examine the differential effects of PGs on sensory neurons. Techniques employed include cell culture, immunocytochemistry, image analysis, biochemical methods, and molecular biology. The experimental focus is on animal models, such as chicken and/or rodent dorsal root ganglion neurons, retinal ganglion cell neurons, and hippocampal neurons, as well as the human neuroblastoma cell line, SH-SY5Y.

Representative Publications

Snow, D.M. Mullins, N. and Hynds, D.L. (2001) Nervous system-derived chondroitin sulfate proteoglycans regulate growth cone morphology and inhibit neurite outgrowth: a light, epifluorescence, and electron microscopy study. Microscopy Res. Tech. 54:273-286.

Allen, W.R., T. S., McClintock, D.L. Hynds, Snow, D.M. (2001) Neuronal contact with chondroitin sulfate proteoglycan modulates outgrowth-regulatory proteins. Proc. Natl Conf.Undergra.d Res. Vol. 15, Sep.

Hynds, D.L. and Snow, D.M. (2001) Fibronectin or laminin elicits differential behaviors from SH-SY5Y growth cones contacting chondroitin sulfate proteoglycans. J. Neurosci. Res. 66:630-642.

Snow, D. M., Smith, J.D., and. Gurwell, J. A. (2002) Binding characteristics of chondroitin sulfate proteoglycans and laminin-1, and correlative neurite outgrowth behaviors in a standard tissue culture choice assay. J. Neurobiol 51:285-301.

Hynds D. L. and Snow D. M. (2002) A semi-automated image analysis method to quantify neurite preference/axon guidance on a patterned substratum. J. Neurosci. Methods 121(1):53-64.

Hynds, D. L., Inokuchi, J-i, and Snow, D.M. (2002) L- and D- threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) inhibit neurite outgrowth from SH-SY5Y cells. Neuroscience 114(3):731-744.

Johnson, W.E., Caterson,B, Eisenstein, S.M., Hynds, D.L., Snow, D. M., and Roberts, S. (*shared senior authorship: D.M. Snow and S. Roberts). (2002) Human intervertebral disc aggrecan inhibits nerve growth in vitro. Arthritis and Rheumatism 46(10):2658-2664.

Snow, D.M., Smith, J.D., Cunningham, A. T., McFarlin, J., and Goshorn E.C. Neurite elongation on chondroitin sulfate proteoglycans is characterized by axonal fasciculation. (2003) Exp. Neurol. 182:310-321.

Hynds, D.L., Spencer, M., Andres, D., and Snow, D.M. (2003) Rit promotes MEK-independent neurite branching in human neuroblastoma cells. J. Cell Sci. 116:1925-1935.

Carman, H.M., Booze, R.M., Snow, D.M., and Mactutus, C.F. (2003) Proximal versus distal cue utilization in preweanling spatial localization: The influence of cue number and location. I., 79(2):157-165.

Hynds, D.L., Rangappa, N Beest, J.T., Snow, D.M., Rabchevsky, A.G. (2004) Microglia Enhance Dorsal Root Ganglion Outgrowth in Schwann Cell Cultures. Glia 46:218-226.

Foltz, T., Carman, H.M., Welch, M.A., Snow, D.M., Strupp, B.J, Booze, R.M and Mactutus, C.M. (2004) Prenatal IV. Cocaine and the HR-OR: a dose-response study. Int'l J. Develop. Neurosci. 22:285-296.

Snow, D.M., Smith, J.D., Booze, R.M., Welch, M., and Mactutus, C.F. (2004) Cocaine-induced inhibition of outgrowth in locus coeruleus neurons is related to gestational exposure period and offspring sex. Int'l J. Develop. Neurosci. 22:297-308.