Domain-specific olivocerebellar projection regulated by the EphA-ephrin-A interaction.
Neural maps in the vertebrate central nervous system often show discontinuously segregated, domain-to-domain patterns. However, the molecular mechanism that establishes such maps is not well understood. Here we show that in the chicken olivocerebellar system, EphA receptors and ephrin-As are expressed with distinct levels and combinations in mapping domains. When ephrin-A2 is retrovirally overexpressed in the cerebellum, the olivocerebellar map is disrupted, excluding axons with high receptor activity from ectopic expression domains. Conversely, overexpression of a truncated EphA3 receptor in the cerebellum reduces endogenous ligand activity to undetectable levels and causes aberrant mapping, with high receptor axons invading high ligand domains. In vitro, ephrin-A2 inhibits outgrowth of inferior olive axons in a region-specific manner. These results suggest that Eph receptors and ephrins constitute domain-specific positional information, and the spatially accurate receptor-ligand interaction is essential to guide inferior olive axons to their correct target domains.
Nishida
Kazuhiko
K
Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Flanagan
John G
JG
Nakamoto
Masaru
M
D000818:Animals; D001369:Axons; D002460:Cell Line; D002462:Cell Membrane; D002490:Central Nervous System / Q000196:embryology; D002531:Cerebellum / Q000378:metabolism; D002645:Chickens; D006801:Humans; D017403:In Situ Hybridization; D008024:Ligands; D008954:Models, Biological; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011689:Purkinje Cells / Q000378:metabolism; D036104:Receptor, EphA2 / Q000378:metabolism*; D036121:Receptor, EphA3 / Q000096:biosynthesis / Q000378:metabolism*; D036081:Receptors, Eph Family / Q000378:metabolism*; D012190:Retroviridae / Q000235:genetics; D013997:Time Factors
D008024:Ligands; D036104:Receptor, EphA2; D036121:Receptor, EphA3; D036081:Receptors, Eph Family