Differentiation and Axonal Outgrowth Pattern of Fetal Dorsal Root Ganglion Cells Orthotopically Allografted into Adult Rats

Abstract

Fetal allogeneic dorsal root ganglia (DRG) between 13 and 15 days (E13-E15) were transplanted into the enucleated fourth and fifth lumbar (L4, L5) ganglionic capsules of adult rat hosts. Some of the grafts were prelabeled with the vital carbocyanine dye Dil. Three to 9 months later, neuroanatomic tracers were applied singly or in combination to the sciatic nerve at a transection site 2-3 cm distal to the ganglion and to the dorsal quadrant of the spinal cord. Tissues in selected cases were stained with antibodies to calcitonin gene-related peptide (CGRP) or to neurofilament protein (antibody RT-97) as evidence of neuronal differentiation and axonal growth. In two grafted animals serial sections were made across the root-cord junction which was examined by light and electron microscopy. This material was compared to similarly prepared sections from two nongrafted animals subjected to dorsal root crush. Some grafted ganglion neurons survived for the 3-9 months of the study. Many of these cells became labeled after tracers were applied to the peripheral nerve, to the lumbar spinal cord, or to both. Additional signs of differentiation included expression of CGRP and neurofilament protein immunoreactivity in neuronal cell bodies and processes. Electron microscopic examination showed many small diameter fibers, both myelinated and unmyelinated, in the grafted root on both sides of the PNS/CNS junction. The results with this orthotopic transplantation model show that fetal DRG neurons can differentiate in an adult host and grow axonal branches into peripheral nerves as well as centrally through the dorsal root toward the spinal cord. In addition, our findings suggest that some of the centrally growing fibers cross the PNS/CNS border into the mature spinal cord.