The present proposal is based upon our discovery that astrocytes from diverse areas of the mammalian CNS express characteristics of multipotent neural stem cells (NSCs), since they can form multipotent neurospheres in vitro. Most astrocytes lose these characteristics after a critical period of postnatal development; however astrocytes from the subependymal zone (SEZ) remain multipotent even into adulthood, and divide to maintain a large pool of neuronal precursors in this region. We propose two sets of experiments to further characterize and analyze the NSC attributes of astrocytes: 1) transplantation of astrocyte-derived neurospheres to a variety of CNS regions in order to test their ability to migrate, integrate, and generate neuronal progeny in different environments; and 2) transplantation of pre-and post-critical period astrocytes into the adult SEZ to test for the presence of factors in this region that direct astrocytes to generate neuronal progeny.
