Nature Neuroscience
3, 1091 - 1097 (2000)
doi:10.1038/80606
Disruption of Eph/ephrin signaling affects migration and proliferation in the adult subventricular zoneJoanne C. Conover1, 2, 5, Fiona Doetsch1, Jose-Manuel Garcia-Verdugo3, Nicholas W. Gale4, George D. Yancopoulos4
& Arturo Alvarez-Buylla11
The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA
2
Ecole Normale Superieure, CNRS URA 1414, 46 rue d'Ulm, Paris, France
3
Universidad de Valencia, Burjasot, Valencia, Spain
4
Regeneron Pharmaceuticals, Inc., 777 Old Saw Mill River Road, Tarrytown, New York 10804-6707, USA
5
Present address: The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609, USA
Correspondence should be addressed to Joanne C. Conover jcc@jax.orgThe subventricular zone (SVZ) of the lateral ventricles, the largest remaining germinal zone of the adult mammalian brain, contains an extensive network of neuroblasts migrating rostrally to the olfactory bulb. Little is known about the endogenous proliferation signals for SVZ neural stem cells or guidance cues along the migration pathway. Here we show that the receptor tyrosine kinases EphB1−3 and EphA4 and their transmembrane ligands, ephrins-B2/3, 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 signaling is involved in the migration of neuroblasts in the adult SVZ and in either direct or indirect regulation of cell proliferation.
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