We propose to identify and characterize the cellular element(s) of PNS responsible for the miliue that supports CNS and PNS axonal regeneration. Evidence from experiments in which PNS nerve was used to bridge regions of CNS shows that CNS and PNS axons are not demonstrably different in their regeneration potential but that their local environments play a decisive role in the success or failure of axonal regeneration after injury. In the PNS, transected sciatic nerve axons will regenerate through an initially-empty tube if the proximal and distal stumps are inserted into the ends. Regeneration into the tube fails if the distal stump is omitted from the tube and the end is closed off. However, we found that a heterogeneous population of cultured PNS cells from embryonic dorsal root ganglia placed inside the tube will support axonal regeneration in the absence of the distal stump -- an indication that these cells can mimic the effect of the distal stump in providing the proper miliue for axonal regeneration. We propose to extend this work by implanting pure populations and defined mixtures of cultured PNS cells (endoneurial fibroblasts, Schwann cells and neurons) to identify the cellular source of the influence. The spatial/temporal events in axonal regeneration through tubes containing cultured cells and the fate of cultured cells in implants will be studied. Culture medium, conditioned by PNS cells, will be tested for an influence on regrowing axons through the tube implants. The mechanism of the influence will be characterized by using specially-designed tubes to provide regenerating axons with alternate environments in which to grow. We will test a mixture of CNS and PNS glial cells to determine if CNS cells actively inhibit axon regrowth.
| Readhead, C; Popko, B; Takahashi, N et al. (1987) Expression of a myelin basic protein gene in transgenic shiverer mice: correction of the dysmyelinating phenotype. Cell 48:703-12 |
