Selective Expression of Insulin-like Growth Factor II in the Songbird Brain

Neuronal replacement occurs in the forebrain of juvenile and adult songbirds. To address the molecular processes that govern this replacement, we cloned the zebra finch insulin-like growth factor II (IGF-II) cDNA, a factor known to regulate neuronal development and survival in other systems, and examined its expression pattern by in situ hybridization 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 magnocellular nucleus of the neostriatum (mMAN), which projects to HVC, and to a lesser extent in the robust nucleus of the archistriatum (RA), which receives projections from HVC. IGF-II mRNA expression was developmentally regulated in zebra finches. In canary HVC, monthly changes in IGF-II mRNA expression covaried with previously reported monthly differences in neuron incorporation. Combining retrograde tracers with in situ hybridization and immunocytochemistry, we determined that the HVC neurons that project to area X synthesize the IGF-II mRNA, whereas the adjacent RA-projecting neurons accumulate the IGF-II peptide. Our findings raise the possibility that within HVC IGF-II acts as a paracrine signal between nonreplaceable area X-projecting neurons and replaceable RA-projecting neurons, a mode of action that is compatible with the involvement of IGF-II with the replacement of neurons. Additional roles for IGF-II expression in songbird brain are likely, because expression also occurs in some brain areas outside the song system, among them the cerebellar Purkinje cells in which neurogenesis is not known to occur.