SCoBIRC FACULTY

Diane M. Snow, Ph.D.

Professor, Department of Anatomy & Neurobiology

Endowed Chair, Spinal Cord and Brain Injury Research Center
Director, Office of Undergraduate Research

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

NIH supported training: http://neuroscienceblueprint.nih.gov/bp_nih-supported_training/stories.htm

The Snow Lab

Dr. Snow and her lab

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 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. 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. Importantly, CSPGs are upregulated following central nervous system(CNS) injury where they contribute to failed 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 CNS system injury.

In an effort to understand the regulatory mechanism(s) governing growth cone migration by CSPGs, both during development and following CNS 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 the neuronal 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.

Many laboratories routinely use a variety of assays in vitro to grossly determine choices neuronal growth cones make as they elongate. We have developed a novel methodology that allows for assessing subtle growth cone behaviors that correlate with neuronal inhibition, permitting a more "holistic" view of growth cone responses to substratum-bound molecules. We have termed this technique the "Inhibitory Quotient System", or "IQ System". In brief, using time-lapse video-microscopy, we record neuronal growth cones as they elongate on a growth-promoting substrata, typically laminin, then interact with the inhibitory proteoglycan in question, either adsorbed in purified form to a tissue culture surface, or expressed by endogenous cells (e.g. reactive astrocytes). A frame-by-frame analysis of neuronal responses (morphologies as well as behaviors) that results in a composite score determines the inhibitory potency for a given CSPG. Score comparisons can be made between various CSPG samples that reflect their differing structures. Currently, we are determining structural differences between CSPGs using FACE analysis. Using this approach, we are amassing extensive detail about each facet of growth cone behavior and the micro-structures of CSPGs that induce growth cone inhibition.

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.

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.

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.

Zhang, G. ,R.-L. Lin, M. Wiggers, D.M. Snow, and L.-Y. Lee. Altered expression of TRPV1 and sensitivity to capsaicin in pulmonary myelinated afferents following chronic airway inflammation in the rat. J. Physiol. (Lond) 586:5771-86, 2008. (PMID: 18832423)

Curinga G, Snow DM, Smith GM. (2008) Mechanisms regulating interpretation of guidance cues during development, maturation, and following injury. [Invited Review] Reviews in the Neurosciences 19 (4-5): 213-26. (PMID: 19145984)

Diane M. Snow

Contact Information

University of Kentucky
Department of Anatomy and Neurobiology

Tel: (859) 323-2613
Fax: (859) 323-5946
E-mail: dsnow@uky.edu