Comparative Strategies of Subependymal Neurogenesis in the Adult Forebrain

Summary

Neuronal precursor cells persist in the forebrain of a wide variety of adult vertebrates, and have been found in cultures derived from fish, birds, rodents and humans. These cells reside within the peri-ventricular ependymal/subependymal zone (SZ), rather than the brain parenchyma. In vivo, these precursors may generate neurons that are recruited to restricted regions, such as the avian neostriatum and mammalian olfactory bulb. In the neurogenic songbird vocal control region, the higher vocal center (HVC), the survival of new neuronal daughter cells is dictated by the environment into which they migrate; both humoral and contact-mediated signals modulate neuronal survival, and these signals are themselves modulated by serum-borne gonadal steroids. In tissue cultures of the adult mammalian SZ, neuronal precursor cells have similarly been found to be widely distributed, and more so than suggested by the limited distribution of actual neurogenesis in vivo. In the adult rat brain, neurons arise from SZ explants derived from much of the lateral ventricular system, including a wide area not known to generate neurons in vivo. In primates, although the postnatal forebrain SZ largely ceases neurogenesis in vivo, it too retains the capacity for neuronal production in vitro, as demonstrated in explants of adult human temporal lobe SZ. The in vitro survival of newly generated neurons is regulated in part by two members of the neurotrophin family, BDNF and NT-4. BDNF in particular may modulate both neuronal specification and survival, in a dose- dependent fashion. Together, these findings suggest the persistence into adulthood of a relatively widespread pool of SZ progenitor cells that remain neurogenic in selected regions but more generally become vestigial, perhaps as a result of the loss of permissive signals for daughter cell migration and/or survival in the local environment.