Conclusions And Future Prospects

Our understanding on the role of ephrins and Eph receptors in synapses has grown considerably during the last 5 years. Not only have these studies affirmed the early speculation that the ephrin-Eph signaling system operates in synapses, they have also exposed its naïveness; these molecules turned out to function in a way much more complicated and diverse than that had initially been speculated. Accordingly, it would not be surprising to see yet other novel physiological and neurobiological effects of these molecules and additional downstream signaling pathways. With regard to downstream signaling pathways, it will be necessary to determine which pathway is more physiologically relevant to a given phenomenon than the others.

More long-term, and medically important question is whether dysfunction of ephrins and Eph receptors may underlie some neuropsychiatric and mental disorders. Abnormal spines have been reported in patients of mental retardation, autism, and other cognitive disorders60-63. Dysfunction of glutamatergic synapses has been implicated in autism and schizophrenia64,65. Since many of ephrins and Eph receptors play important developmental roles, null mutations are likely to result in severe developmental phenotypes or even fetal death, as seen in several knockout mouse models. Therefore, epigenetic dysfunction of ephrins and Eph receptors may be more clinically relevant. In this vein, it is interesting to note that administration of drugs of abuse induces a significant elevation in the expression of ephrinB2 in the nucleus accumbens66 and EphBl in the striatum67. These drugs also cause long-lasting changes in the structures of dendrites and dendritic spines68,69. The possible role of ephrins and Eph receptor in the development of drug addiction and other nongenetic disorders would thus be one of the important research topics in the near future.*

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