SELECTIVE EXPRESSION OF INSULIN-LIKE-GROWTH-FACTOR-II IN THE SONGBIRDBRAIN

Neuronal replacement occurs in the forebrain of juvenile and adult son gbirds. To address the molecular processes that govern this replacemen t, we cloned the zebra finch insulin-like growth factor II (IGF-II) cD NA, a factor known to regulate neuronal development and survival in ot her systems, and examined its expression pattern by in situ hybridizat ion and immunocytochemistry in juvenile and adult songbird brains. The highest levels of IGF-II mRNA expression occurred in three nuclei of the song system: in the high vocal center (HVC), in the medial magnoce llular nucleus of the neostriatum (mMAN), which projects to HVC, and t o a lesser extent in the robust nucleus of the archistriatum (RA), whi ch receives projections from HVC. IGF-II mRNA expression was developme ntally regulated in zebra finches. In canary HVC, monthly changes in I GF-II mRNA expression covaried with previously reported monthly differ ences in neuron incorporation. Combining retrograde tracers with in si tu hybridization and immunocytochemistry, we determined that the HVC n eurons that project to area X synthesize the IGF-II mRNA, whereas the adjacent RA-projecting neurons accumulate the IGF-II peptide. Our find ings raise the possibility that within HVC IGF-II acts as a paracrine signal between nonreplaceable area X-projecting neurons and replaceabl e RA-projecting neurons, a mode of action that is compatible with the involvement of IGF-II with the replacement of neurons. Additional role s for IGF-II expression in songbird brain are likely, because expressi on also occurs in some brain areas outside the song system, among them the cerebellar Purkinje cells in which neurogenesis is not known to o ccur.