UK Department of Anatomy and Neurobiology

Faculty Research

DIANE M. SNOW, Ph.D.
Case Western Reserve University, Cleveland, OH (1990)
Postdoctoral training at The University of Minnesota, Minneapolis, MN
Professor of Anatomy and Neurobiology
Endowed Chair, Spinal Cord and Brain Injury Research Center (SCoBIRC)

Research Interests: Neuronal Growth Cone Guidance, Extracellular Matrix Molecules, Regeneration

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. Th Inhibition of neurite outgrowth e direction of axonal extension is accomplished by the growth cone - the sensorimotor structure at the distal tip of the elongating axon. 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. The research in Dr. Snow’s laboratory focuses on a class of ECM molecule, the proteoglycans, specifically the chondroitin sulfate proteoglycans (CSPGs), and their effect on migrating growth cones and regeneration. CSPGs are located in regions where axons do not grow in vivo, and act as inhibitors of neurite outgrowth in vitro and in vivo. Further, CSPGs are upregulated following nervous system injury where they prevent nerve regeneration. An understanding of the mechanisms by which CSPGs inhibit outgrowth 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 of the Snow lab 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 theneuronal cytoskeleton in growth cone turning in response to contact with inhibitory molecules, and 3) examine the differential effects of CSPG structure on sensory neurons, using “Designer PGs” and a novel evaluation technique called the “Inhibitory Quotient (IQ)” system. 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 serotonergic neurons, as well as on a variety of cell lines.

Representative Publications

*Wilson, M.T. and Snow, D.M. (2000) Chondroitin sulfate proteoglycan expression pattern in hippocampal development: potential regulation of axon tract formation. J. Comp. Neurol.424:532-546.

*Snow, D.M., Smith, J.D., Welch, M.A., Booze, R., Mactutus, C. M. (2001) Cocaine alters locus coeruleus neuron outgrowth in vivo and in vitro. Neurotoxicol. Teratol.23:225-234.

*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. NatlConf.Undergrad. 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., Roberts, S.and Snow, D. M. (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. Phys.&Behav., 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. Glia46:218-226.

*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.

*Dey, S., Booze, R.M., Mactutus, C.F. and Snow, D.M. (2006) Specificity of prenatal cocaine on inhibition of locus coeruleus neurite outgrowth. Neurosci.139(3):899-907.

*Booze, R.M., Wallace, D.R., Silvers, J.M., Strupp, B.J., Snow, D.M., and Mactutus, C.F. (2006) Prenatal cocaine exposure alters alpha2 receptor expression in adolescent rats. BMC Neuroscience 2006, 7:33

*Heron, P., Sutton, B., Curinga, G.M., Smith, G. M. and Snow, D.M. (2007)Localized gene expression of guidance molecules in a co-culture model to direct axonal growth. J. Neurosci. Meth., 159(2):203-214.

*Dey, S., Mactutus^,C.F., Booze^,R.M., and Snow^,D.M. (2007) Prenatal cocaine exposure induces apoptosis in locus coeruleus neurons in vitro by altering the bax/bcl-2 ratio and through caspase-3 apoptotic signaling. Neurosci. 144(2):509-521.

*Curinga, G.M., Snow, D.M., Mashburn, C., Kohler, K., Thobaben, R., Caggiano, A.O., Smith, G.M. (2007) Mammalian-produced chondroitinase AC mitigates axon inhibition by chondroitin sulfate proteoglycans. J Neurochem. 102(1):275-288.39.

*Dey, S. and Snow, D. M. (2007) Prenatal cocaine exposure induces apoptosis in locus coeruleus neurons through TNF-a mediated induction of Bax and JNK-1-MAPK pathways. J Neurochem. 103(2):542-556.

*Curinga, G.M.,D M Snow, and G M Smith (2008) “Mechanisms regulating interpretation of guidance cues during development, maturation, and following injury”, Reviews in the Neurosciences- In press.

e-mail: dsnow@uky.edu
Phone: (859)323-2613
Fax: (859)323-5946

*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.

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.