The rostral migratory stream (RMS) is a unique pathway responsible for transporting new neurons from the ventricular zone-subventricular zone (VZ-SVZ) stem cell niche through the anterior forebrain to the olfactory bulb (OB). In rodents, the RMS supplies new neurons to the OB throughout life. In human neonatal development, VZ-SVZ neurogenesis supports RMS-OB migration and another forebrain pathway the medial migratory stream (MMS) that supplies new neurons to the ventromedial prefrontal cortex. The organization of the RMS, which has been well characterized, consists of tightly arrayed chains of migratory neuroblasts within a dense meshwork of astrocytes, presenting a unique organization that supports controlled, large-scale and long-range neuroblast migration. We found that the Eph receptor, EphA4, is essential for initially establishing and then maintaining RMS cytoarchitecture, as well as mediating efficient neuroblast transit to the OB. Eph-ephrin signaling is a common mechanism used in development to coordinate axon guidance, cell migration, boundary discrimination and cell segregation through adhesive and repulsive cell contact-mediated signaling interactions. We are currently investigating the role of Eph-ephrin signaling networks in regulating migration and determining the destination of newly generated neurons in the developing and adult brain.