SCHWANN-CELLS AND FETAL TECTAL TISSUE COGRAFTED TO THE MIDBRAIN OF NEWBORN RATS - FATE OF SCHWANN-CELLS AND THEIR INFLUENCE ON HOST RETINALINNERVATION OF GRAFTS

Schwann cells transplanted into the adult central nervous system (CNS) can exert powerful growth-promoting effects on damaged axons. An impo rtant issue is whether central axons induced to regrow by Schwann cell s retain the capacity to recognize and selectively innervate their app ropriate target cells. To examine how Schwann cells may influence the specificity of neuron-neuron interactions in CNS neuropil, we cultured neonatal rat Schwann cells and mixed them with dissociated fetal tect al cells. In some instances, Schwann cells were prelabeled with Hoechs t dye 33342. Schwann cells comprised between 2.5 and 15% of the combin ed cell population. After reaggregation, cografts were injected onto t he midbrain of newborn rats. One to 6 months later, grafts were examin ed for the presence of Schwann cells and the pattern and density of ho st retinal innervation of the cografts was assessed. Immunohistochemic al studies showed that areas of the transplants containing large numbe rs of surviving Hoechst-labeled Schwann cells were strongly immunoreac tive for the low-affinity nerve growth factor receptor (p75), S-100, G FAP, and laminin. Very little peripheral (P-o positive) myelin was see n. As in pure fetal tectal grafts, host retinal axons were sometimes o bserved to innervate superficial, localized areas in the cografts know n to be homologous to the retinorecipient layers of the superior colli culus. Unlike pure tectal grafts, however, optic axons were not confin ed to these regions and fibers were often dispersed within the cograft neuropil. Dense growth was seen in association with Hoechst-labeled S chwann cells and, in some cases, optic axons were observed to grow tow ard Schwann cells and away from nearby target areas. These observation s suggest that, under certain circumstances, Schwann cells can stimula te retinal axons to grow into inappropriate (nontarget) regions in the CNS, presumably by producing growth promoting factors which mask or c ompete with signals released from the target neurons themselves. (C) 1 995 Academic Press, Inc.