Migration Patterns of Neonatal Subventricular Zone Progenitor Cells Transplanted into the Neonatal Striatum

Abstract

Our previous studies have shown that the progeny of the neuronal progenitor cells localized in a discrete region of the anterior part of the neonatal subventricular zone, referred to as the SVZa, migrate tangentially along a stereotypical and extended pathway to the olfactory bulb, and then turn radially into one of the overlying cellular layers. In this study we have examined whether the SVZa cells retain their ability to migrate and disperse when heterotopically transplanted into the striatum. SVZa cells from P0–P2 rat pups were microdissected, dissociated, labeled with the lipophilic, fluorescent dye PKH26 or the cell proliferation marker BrdU, and then transplanted into the neonatal (P0–P2) striatum. Examination of the striatum a few days after transplantation revealed aggregates of heavily labeled BrdU-positive, SVZa cells in the striatum, often situated near blood vessels. Two to four weeks after transplantation, however, the labeled SVZa cells had disseminated from their site of implantation and showed three patterns of distribution. In none of the cases was the implantation site detectable in the striatum, signifying that the cells had become incorporated in the host brain. Of the 12 brains analyzed for cell distribution, transplanted SVZa cells were confined to the striatum in 4 cases. The cells were present as individual cells or in small groups of usually two to four cells. When PKH26 was used, we found that many of the transplanted cells extended processes into the striatum. In 3 out of the 12 animals, the labeled SVZa cells were distributed along the dorsal and lateral aspects of the striatal boundary. In the remaining five animals, labeled SVZa cells appeared in both locations: within the striatum as well as along the striatal boundary. The dispersion of the transplanted cells within the striatum and the presence of the transplanted SVZa cells all along the striatal boundary, a region corresponding to the lateral cortical stream of migration of the developing forebrain, demonstrates that the isochronically transplanted SVZa cells retained their capacity to migrate.