A Comparison of the Patterns of Migration and the Destinations of Homotopically Transplanted Neonatal Subventricular Zone Cells and Heterotopically Transplanted Telencephalic Ventricular Zone Cells

Abstract

The cells arising in the anterior part of the subventricular zone (SVZa) migrate along a well-demarcated pathway which lacks radial glial fibers to the olfactory bulb where they differentiate into interneurons of the granule cell layer or glomerular layer (Luskin, 1993, Neuron 11, 173). To analyze the mechanisms underlying this highly directed migration, we have compared the migratory behavior of unmanipulated SVZa-derived cells to that of homotopically transplanted SVZa cells and of heterotopically transplanted telencephalic ventricular zone (VZ) cells that ordinarily migrate in association with radial glial fibers. To identify the phenotype of the SVZa progenitor cells prior to their transplantation, we characterized them in vitro using cell type-specific markers. After 1 day in culture nearly all the SVZa cells were stained with TuJ1, a neuron-specific marker; only an occasional cell exhibited a glial phenotype as judged by the presence of GFAP-immunoreactivity. This indicates that SVZa cells express a neuronal phenotype. To reveal the spatiotemporal distribution of homotopically transplanted neonatal SVZa cells in a host brain, dissociated SVZa cells from Postnatal Day 0 (P0)-P2 animals were labeled with the lipophilic dye PKH26 or the cell proliferation marker BrdU and implanted into the SVZa of host animals of the same age. Within the first week after transplantation there were vast numbers of labeled cells throughout the pathway. Over the next 2 weeks the labeled cells migrated into the overlying cellular layer of the olfactory bulb and began to differentiate, and within 4 weeks the transplanted cells had reached their final positions in the granule cell and glomerular layers of the olfactory bulb in the same proportions as for unmanipulated SVZa-derived cells. While en route to the olfactory bulb the homotopically transplanted cells never strayed from the migratory pathway. In contrast, heterotopically transplanted VZ cells from the embryonic telencephalon did not undergo migration although they did differentiate. These results demonstrate that the homotopically transplanted SVZa-derived cells adopt a mode of migration indistinguishable from that ordinarily utilized by SVZa-derived neurons and that the VZ cells are unable to decipher the same set of guidance cues.

Region-specific differentiation of neural tube-derived neuronal restricted progenitor cells after heterotopic transplantation

“…3 E and F), confirming that NRP cells do not adopt astroglial or oligodendrocyte identities. This finding is in distinct contrast to other neural progenitors, which predominantly mature into glia after transplantation (8,26,27), but similar to SVZa neuronal progenitors, which retain their neuronal identity following heterotypic transplantation (20,25).…”

“…Such lineage-restricted precursors (glial restricted and neuronal restricted progenitors, GRPs and NRPs, respectively) have been identified (9,10). Progenitor cells have been isolated and characterized from multiple brain regions (2)(3)(4)(11)(12)(13)(14)(15) whereas NRP cells have so far been identified in only a few locations (2,(16)(17)(18)(19)(20)(21)(22)(23).…”

Cell migration in the postnatal subventricular zone

“…Or is that capacity exclusive of the SVZ cells? While the SVZ/RMS could sustain migration of some exogenous progenitor cell populations (61)(62)(63), cells from the embryonic ventricular zone and external granular layer failed to migrate when transplanted into the postnatal SVZ (57,64). In spite of their normal radial migration it could be expected that external granular layer and ventricular zone cells would respond to the local cues of the postnatal SVZ/RMS, for, as we have seen above, many factors involved in radial migration are also present in RMS migrating cells.…”

Basic and clinical neuroscience applications of embryonic stem cells

“…The majority of homotopically and isochronically transplanted cells could follow host-derived differentiation and migration signals and displayed appropriate patterns of integration. However, despite their normally broad differentiation potential, heterochronically transplanted VZ cells failed to exhibit normal migratory behavior in the absence of radial glia (Zigova et al, 1996).…”

“…The developmental age of donor and recipient cells, the source of NSCs, the methods of in vitro cellular expansion and differentiation, and the area into which donor cells will be transplanted are additional variables that determine the fate of the engrafted cells (Brustle, 1999;Auerbach et al, 2000;Zigova et al, 1996;Onifer et al, 1997;Sheen and Macklis, 1995;Sheen et al, 1999;Catapano et al, 1999). populations that will be compatible with the specialized needs of the damaged/diseased nervous system.…”