THE ADULT CNS RETAINS THE POTENTIAL TO DIRECT REGION-SPECIFIC DIFFERENTIATION OF A TRANSPLANTED NEURONAL PRECURSOR CELL-LINE

The chronic survival and differentiation of the conditionally immortal ized neuronal cell line, RN33B, was examined following transplantation into the adult and neonatal rat hippocampus and cerebral cortex. In c lonal culture, differentiated RN33B cells express p75(NTR) and trkB mR NA and protein, and respond to brain-derived neurotrophic factor treat ment by inducing c-fos mRNA. Transplanted cells, identified using immu nohistochemistry to detect beta-galactosidase expression, were seen in most animals up to 24 weeks posttransplantation (the latest time poin t examined). Stably integrated cells with various morphologies consist ent with their transplantation site were observed. In the cerebral cor tex, many RN33B cells differentiated with morphologies similar to pyra midal neurons and stellate cells. In the hippocampal formation, many R N33B cells assumed morphologies similar to pyramidal neurons character istic of CA1 and CA3 regions, granular cell layer neurons of the denta te gyrus, and polymorphic neurons of the hilar region. Identical morph ologies were observed in both adult and neonatal hosts, although a gre ater percentage of beta-galactosidase immunoreactive cells had differe ntiated in the neonatal brains. These results suggest that RN33B cells have the developmental plasticity to respond to local microenvironmen tal signals and that the adult brain retains the capacity to direct th e differentiation of neuronal precursor cells in a direction that is c onsistent with that of endogenous neurons.