November 19, 2004

Title: Role of Heparan sulfate in neuronal development

Dr. Eric Shipp
Department of Biology,
California Institutes of Technology

Abstract: Axonal guidance and neuronal migration are processes whereby axons and
neurons are biochemically directed throughout the central nervous system in
a developing organism. During this critical developmental stage, axons must
travel considerable distances in a very ordered fashion. Heparan sulfate
proteoglycans (HSGs) are negatively charged, sulfated polysaccharides found
on the cell surface and in the extracellular matrix. Recent studies suggest
that HSGs play an integral role in promoting the activity of Slit, a family
of secreted neuronal guidance proteins. Slit initiates axonal repulsion by
binding to the cell surface receptor, Roundabout (Robo). Removal of cell
surface HSGs abolishes the chemorepulsive response of Slit toward growing
axons and migrating neurons. However, the precise mechanism by which HSGs
promote Slit-mediated processes is not well understood. However, the
sulfation of the 2,3, and 6 positions of heparan sulfate are thought to be
important for the specificity of these interactions. We have identified the
sulfate groups required for these interactions using a native gel shift
assay and neuronal migration assays.