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The Journal of Neuroscience, November 15, 1999, 19(22):10026-10035

Selective Inhibition of Spinal Cord Neurite Outgrowth and Cell Survival by the Eph Family Ligand Ephrin-A5

Yong Yue^{1, 2}, Jianying Su¹, Douglas Pat Cerretti³, Gary M. Fox⁴, Shuqian Jing⁴, and Renping Zhou^{1, 2}

¹ Laboratory for Cancer Research, College of Pharmacy, Rutgers University, Piscataway, New Jersey 08854, ² Department of Neuroscience and Cell Biology, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, ³ Immunex Research and Development Corporation, Seattle, Washington 98101, and ⁴ Amgen, Incorporated, Thousand Oaks, California 91320

The Eph family tyrosine kinase receptors and their ligands, the ephrins, have been shown to play critical roles in cell migration, tissue morphogenesis, and axonal guidance in many different systems. However, their function in the spinal cord has not been examined carefully. We showed in this study that several Eph receptors, including EphA3, Eph A4, and Eph A5, are expressed in the ventral spinal cord in partially overlapping patterns, with EphA5 exhibiting the most widespread transcription in the entire ventral spinal cord during early development. Complementary to the receptor expression, a ligand of these receptors, ephrin-A5, is transcribed in the dorsal half of the spinal cord. Consistent with the spatial location of receptor expression, the ligand selectively inhibits neurite outgrowth and induces cell death of the ventral, but not the dorsal, spinal cord neurons. These observations suggest that interactions between the Eph family receptors and ligands exerts negative influences on ventral spinal cord neurons and thus may play important roles in regulating morphogenesis and axon guidance in the spinal cord.

Key words: Eph family receptors; ephrins; neurite outgrowth; spinal cord; apoptosis; in situ hybridization

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Copyright © 1999 Society for Neuroscience  0270-6474/99/192210026-10$05.00/0

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