Astroglial Boundary Formation and EphA4 Signaling in Neuroblast Migration

Adult neurogenesis, the process of generating new neurons from neural precursors, is a highly complex process that is limited to two specific areas of the brain, the dentate gyrus of the hippocampus and the subventricular zone (SVZ). Despite continued research investigating neurogenesis in these two regions, we still lack a fundamental understanding of the molecular mechanisms of neural cell division, migration, differentiation, and integration in the postnatal brain. In particular, the rostral migratory stream (RMS), which is a cellular migratory route for newly generated neuronal precursors that travel from the SVZ to the olfactory bulb, will provide a useful model to address these critical questions concerning postnatal neurogenesis and cell migration. Specifically, research involving the class of membrane-bound proteins known as Ephs and ephrins, which have many regulatory roles in development that persist in postnatal neurogenic regions, has helped to elucidate the complex regulatory network that governs neural stem cell migration in the developing RMS. Currently, it has been suggested that Ephs and ephrins are key regulators of RMS development, as they participate in contact mediated signaling involved in regulating the migration of neural cell precursors from the SVZ to the olfactory bulb. Out of this large class of receptor tyrosine kinases (Ephs) and associated ligands (ephrins), the receptor EphA4 appears to maintain this restriction and play a crucial role in regulating proper RMS development in mammals. Research performed has helped determine the expression profile of EphA4 in this developing brain region, its crucial role in organizing astrocytes around tangentially migrating stem cells in the RMS, and its role in cellular proliferation