BMP-2-dependent integration of adult mouse subventricular stem cells into the neural crest of chick and quail embryos

Central nervous system (CNS) stem cells isolated from the subventricular zone (SVZ) show a remarkable differentiation potential into neural derivatives. Surprisingly adult SVZ cells can also be induced in vitro to differentiate into neural crest cell fates. This fate switch is dependent on the combination of fibroblast growth factor 2 (FGF2) and bone morphogenetic proteins (BMPs). Here we transplanted adult SVZ stem cells from GFP mice as neurospheres into the trunk neural tube of chick and quail embryos. Only neurospheres pre-exposed to BMP-2 and FGF2 formed close contacts with the dorsal neuroepithelium corresponding to the neural crest area. GFP-positive cells emigrated from the neurosphere and were identified in the roof plate, the dorsal neuroepithelium and among emigrating neural crest cells adjacent to the neural tube. Neurospheres not treated with BMP-2 did not integrate into the neuroepithelium. Our data demonstrate that adult CNS stem cells can be efficiently prepared in vitro for integration into the embryonic neural crest. BMP-2 treatment conveys the necessary morphogenetic capabilities to adult stem cells for future clinical transplantation strategies.