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 neur onal cell migration in the adult mouse forebrain, we have first invest igated the cellular composition of the subventricular zone-olfactory b ulb pathway (SVZ-OB). The pathway was essentially composed of cells wi th neuronal and astrocytic identities, neuronal cells being four times more numerous than astrocytes. Neuronal cells (precursors and some yo ung postmitotic neurons) formed continuous cellular strands of migrato ry cells from the anterior horn of the lateral ventricle to the olfact ory bulb. These chains of migrating cells moved within channels formed by the processes of a special subpopulation of astrocytes. The neuron al cells expressed the embryonic form of polysialic acid neural cell a dhesion molecule, and the astrocytes were tenascin-C positive, thus pr eserving an embryonic cellular environment. Through transplantation ex periments, the second part of this study attempted to analyze the func tional properties of the adult SVZ-OB pathway. Early postnatal (P2-13) cerebellar progenitor cells, taken from a transgenic mouse line in wh ich cerebellar granule cells and molecular layer interneurons (basket/ stellate cells) expressed the reporter gene lacZ, were implanted in th e SVZ-OB pathway of adult wild-type mice. Unlike grafted SVZ cells tha t migrate all along the pathway, none of the cerebellar precursors rea ched the olfactory bulb, although some of them were able to migrate al ong the caudal one-third of the pathway. The majority (over 67%) of th e migrating cells were progenitors that acquired the phenotype of bask et/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 prem igratory neurons. From the two types of grafted cerebellar progenitors , only those with migratory capability and that do not follow radial g lial axes are able to translocate along the SVZ-OB pathway. Furthermor e, the basket/stellate cell progenitors are specified at the time of g rafting: Neither their identity nor the pace of expression of their ma jor distinctive features are influenced by local signals emanating fro m the adult forebrain. (C) 1996 Wiley-Liss, Inc.