William Snider, MD
Professor
Joint appointment in Neurology

Education:

MD, University of North Carolina at Chapel Hill, 1977

Developmental Regulation by Neuronal Growth Factors

Work in my laboratory is directed at the role of neuronal growth factors in the development and regeneration of axons. We employ sensory neurons of the DRG as a model system. Sensory neurons are unique in elaborating a peripheral axon that regenerates readily after injury and a central axon projecting in the spinal cord that does not. This work is directly relevant to a major NINDS goal of achieving spinal cord repair.

We are pursuing 3 important aspects of axon growth regulation by neurotrophins:

Neurotrophin signaling mediators in the development of axon projections: DRG neurons are powerfully regulated by members of the NGF and GDNF families of neuronal growth factors. We have recently defined critical functions for NGF and NT3 in the development of DRG peripheral and central projections (Neuron 25: 345–357; Neuron 38: 403-416). We have also recently shown critical but separable functions for Raf/Erk and PI3K signaling during sensory axon growth in vitro (Neuron 35: 65-76). A major difficulty in this field has been that signaling mediator mutants are embryonic or early postnatal lethal due to abnormalities in development of multiple organs. We have now generated conditional mutant mice where Raf/ERK signaling will be abolished only in DRG neurons. The development of axon projections in these mice is likely to be highly informative.

Neurotrophin signaling and the axon cytoskeleton: In addition to roles in regulating gene transcription, we can expect that neurotrophin signaling mediators will have powerful local actions on the axon cytoskeleton. Using immunolabeling of phosphorylated signaling mediators and real time visualization of GFP-fusion proteins at the growth cone, we are exploring the role of localized PI3 kinase signaling in cytoskeletal regulation. The roles of a variety of PI3K effectors are being determined by electroporation of activated and dominant inhibitory constructs into E13 DRG neurons and assessing effects on NGF-induced axon growth.

Mouse genetic studies of axon regeneration: Neurotrophins have powerful pharmacologic effects on axon growth in adult animals and Schwann cells have long been known to upregulate growth factor synthesis after peripheral nerve injury. Never-the-less, nothing is known about the role of growth factor signaling mediators in axon regeneration, because of early death of mutant mice. Inducible null mutations specific to DRG neurons will be required for this analysis. We have generated an inducible DRG specific Cre line. These have been crossed with floxed allele Raf/Erk lines. We will assess axon regeneration and DRG gene expression after injury.

Bill Snider is Director of the UNC Neuroscience Center. 

Recent Publications:

Ichinose, T. and WD Snider (2000). Differential effects of TrkC isoforms on sensory axon outgrowth.   J.Neurosci.Res. (Special Millennium Issue on Developmental Neurobiology) 59(3):365-71.

Patel TD, Jackman A, Rice F, Kucera J and W.D. Snider (2000). Sensory neuron development in the absence of  NGF/trkA signaling in vivo. Neuron 25(2):345-57.

Keller-Peck CR, Feng G, Sanes JR, Yan Q, Lichtman JW, Snider WD (2001). Glial cell line-derived neurotrophic factor administration in postnatal life results in motor unit enlargement and continuous synaptic remodeling at the neuromuscular junction. J Neurosci. 21(16):6136-46.

Liu RY, and WD Snider (2001). Different signaling pathways mediate regenerative versus developmental sensory axon growth. J Neurosci 21: RC164.

Liu RY, Schmid RS, Snider WD, Maness PF (2002). NGF Enhances Sensory Axon Growth Induced by Laminin but Not by the L1 Cell Adhesion Molecule. Mol Cell Neurosci. 20(1):2-12.

Markus A, Zhong J and WD Snider (2002). Raf and Akt mediate distinct aspects of sensory axon growth. Neuron 35:65-76.

Snider WD, Zhou FQ, Zhong J and A Markus (2002). Signaling the Pathway to Regeneration. Neuron 35: 13-16.

Markus A, Patel TD and WD Snider (2002). Neurotropic factors and axonal growth. Curr Opin Neurobiol 12: 523-531.

Patel TD, Kramer I, Kucera J, Niederkofler V, Jessel TM, Arber S and WD Snider (2003). Peripheral NT3 signaling is required for ETS protein expression and central patterning of proprioceptive afferents. Neuron 38:403-416.

Zhou FQ, Zhong J and WD Snider (2003). Extracellular crosstalk: when GDNF meets N-CAM. Cell 113(7): 814-815.