Subventricular zone-olfactory bulb migratory pathway in the adult mouse: cellular composition and specificity as determined by heterochronic and heterotopic transplantation.

To gain insight into cellular and molecular mechanisms subserving neuronal cell migration in the adult mouse forebrain, we have first investigated the cellular composition of the subventricular zone-olfactory bulb pathway (SVZ-OB). The pathway was essentially composed of cells with neuronal and astrocytic identities, neuronal cells being four times more numerous than astrocytes. Neuronal cells (precursors and some young postmitotic neurons) formed continuous cellular strands of migratory cells from the anterior horn of the lateral ventricle to the olfactory bulb. These chains of migrating cells moved within channels formed by the processes of a special subpopulation of astrocytes. The neuronal cells expressed the embryonic form of polysialic acid neural cell adhesion molecule, and the astrocytes were tenascin-C positive, thus preserving an embryonic cellular environment. Through transplantation experiments, the second part of this study attempted to analyze the functional properties of the adult SVZ-OB pathway. Early postnatal (P2-13) cerebellar progenitor cells, taken from a transgenic mouse line in which cerebellar granule cells and molecular layer interneurons (basket/stellate cells) expressed the reporter gene lacZ, were implanted in the SVZ-OB pathway of adult wild-type mice. Unlike grafted SVZ cells that migrate all along the pathway, none of the cerebellar precursors reached the olfactory bulb, although some of them were able to migrate along the caudal one-third of the pathway. The majority (over 67%) of the migrating cells were progenitors that acquired the phenotype of basket/stellate cells. Granule cell progenitors and most granule cells did not survive transplantation. These results show that the adult SVZ-OB pathway is not a "passive generic guidance" for all classes of premigratory neurons. From the two types of grafted cerebellar progenitors, only those with migratory capability and that do not follow radial glial axes are able to translocate along the SVZ-OB pathway. Furthermore, the basket/stellate cell progenitors are specified at the time of grafting: Neither their identity nor the pace of expression of their major distinctive features are influenced by local signals emanating from the adult forebrain.