Irrespective of the region of isolation NRP cells share several properties: an ability to divide, the expression of polysialated neural cell adhesion molecule, the expression of neuronal markers such as type III -tubulin and microtubule-associated protein 2 (MAP-2), and an inability to generate glial derivatives in conditions in which other precursors readily generate astrocytes and oligodendrocytes. The neuronal lineage commitment of the NRPs seems immutable and is in contrast to progenitor populations described by Roy et al. (24), where oligodendrocyte precursors in vitro generated a small number of type III -tubulin-positive cells.Despite their overall similarities, differences between neural progenitor cells isolated from different brain regions exist (reviewed in ref. 9). For example, progenitors from the hippocampus, but not from the cerebellum or midbrain, produce hippocampal pyramidal neurons. Likewise, Luskin and colleagues (25) have noted that neurons derived from the anterior forebrain subventricular zone (SVZa) undergo GABAergic differentiation when transplanted into the striatum. These and other results raise the possibility that the restriction in developmental potential arises early and cannot be reversed. Multiple classes of NRPs distinguished on the basis of their ability to generate specific subclasses of neurons may exist.In this study, the ability of spinal cord NRP cells to migrate and differentiate after their transplantation into the neonatal SVZa was examined and compared with endogenous and homotypically transplanted SVZa NRP cells. Our results show that spinal cord NRP cells are restricted to generating neurons in vivo. NRPs, however, migrate extensively and incorporate into different brain regions, and subsets of cells synthesize cholinergic, glutaminergic, and GABAergic neurotransmitters. Spinal cord NRPs differ from SVZa-derived NRPs in their migration and differentiation, indicating that cell intrinsic mechanisms play an important role in regulating differentiation.
Materials and MethodsIsolation and Labeling of NRP and GRP Cells. Cells were isolated as described (12). Immunoselected cells were labeled by using an enhanced green fluorescent protein (GFP) retroviral construct (gift from Ray White, University of Utah). The construct was packaged by using the Phoenix cell line (gift from Gary Nolan, Stanford University, Stanford, CA). Viral supernatant was collected from infected cells grown in neuroepithelial basal medium. GFP expression in infected cells (10%) was evident within 48 h in vitro, and its expression persisted for at least 10 days.Transplantation of GFP-Labeled NRP and GRP Cells. The procedure described by Luskin and coworkers (16, 25) was used with slight modifications to transplant cells into the right SVZa of postnatal day 1 rat pups. About 3 l of the GFP-labeled NRP or GRP cell suspension (approximately 3 ϫ 10 4 cells) was injected into the SVZa. The needle was left in position for approximately 3 min and gradually withdrawn, the skull flap was repositioned, and the...