Disruption of Eph/ephrin signaling affects migration and proliferation in the adult subventricular zone

The subventricular zone (SVZ) of the lateral ventricles, the largest remain ing germinal zone of the adult mammalian brain, contains an extensive netwo rk of neuroblasts migrating rostrally to the olfactory bulb. Little is know n about the endogenous proliferation signals for SVZ neural stem cells or g uidance cues along the migration pathway. Here we show that the receptor ty rosine kinases EphB1-3 and EphA4 and their transmembrane ligands, ephrins-B 2/3, are expressed by cells of the SVZ. Electron microscopy revealed ephrin -B ligands associated with SVZ astrocytes, which function as stem cells in this germinal zone. A three-day infusion of the ectodomain of either EphB2 or ephrin-B2 into the lateral ventricle disrupted migration of neuroblasts and increased cell proliferation. These results suggest that Eph/ephrin sig naling is involved in the migration of neuroblasts in the adult SVZ and in either direct or indirect regulation of cell proliferation.