EphA receptors and ephrin-A ligands exhibit highly regulated spatial and temporal expression patterns in the developing olfactory system.

The spatiotemporal expression patterns of the chemorepulsive EphA receptors, EphA4 and EphA7, and three ephrins-A2, A4 and A5, were examined in the developing rat primary olfactory system. Unlike the visual system that has simple and stable gradients of Ephs and ephrins, the olfactory system demonstrates complex spatiotemporal expression patterns of these molecules. Using immunohistochemistry, we demonstrate that expression of these molecules is dynamic and tightly regulated both within and between different cell types. We reveal restricted targeting of these proteins within subcellular compartments of some neurons. EphA4, ephrin-A2 and ephrin-A5 were expressed by primary olfactory axons during the embryonic formation of the olfactory nerve. There were no gradients in expression along the rostrocaudal or ventrodorsal axes in the nasal cavity and olfactory bulb. However, during the early neonatal period, axons expressing different levels of ephrin-A5 sorted out and terminated in a subpopulation of glomeruli that were mosaically dispersed throughout the bulb. The expression of EphA4 and ephrin-A2 was dramatically down-regulated on all axons during the early neonatal period of glomerular formation. The uniform co-expression of receptors and ligands before glomerular formation suggests they play a generic role in axon-axon interactions in the olfactory nerve and nerve fibre layer. In contrast, loss of EphA4 from axons during glomerular formation may facilitate the interaction of ephrin-A5 with Eph receptors on target cells in the bulb. While EphA4, EphA5 and EphA7 are not mosaically expressed by bulbar neurons, other Eph receptors may have expression patterns complementary to the ephrin-A5-positive subpopulation of glomeruli.

Increased expression of EphA7 in inflamed human dental pulp.

INTRODUCTION: Pulpitis has been associated with abundant inflammatory cells, dilated blood vessels, and thickening nerve fibers histopathologically with or without severe pain clinically. On the basis of EphA7 receptor expression in inflammatory cells, the developing mouse dental pulp, and trigeminal nerve system, EphA7 may possibly be involved in local inflammatory response and sensory innervation of adult dental pulp as well as odontogenic pain conducted through the trigeminal system. The purpose of the study was to analyze the expression of EphA7 gene in healthy and inflamed human dental pulps and to elucidate the roles of EphA7 gene in dental pulp inflammation response and odontogenic pain. METHODS: Twelve healthy controls, 5 acute pulpitis from dental trauma, 21 symptomatic, and 20 asymptomatic irreversible pulpitis human dental pulps were involved in the study. The protein expression, subcellular localization, and mRNA level of EphA7 gene were detected by immunohistochemistry and real-time reverse transcriptase-polymerase chain reaction, respectively. RESULTS: In healthy samples, immunohistochemical staining showed positive EphA7 expression only in vascular endothelial cells and odontoblasts with cytoplasm staining. Under inflammatory conditions, in addition to the above cells, EphA7 staining began to occur in fibroblasts, nerve fiber tissues, and inflammatory cells. Compared with healthy samples, EphA7 expressions at both mRNA and protein levels increased significantly in acute and irreversible pulpitis samples. In asymptomatic irreversible pulpitis samples, EphA7 expressions were significantly lower than those in symptomatic ones but still higher than those in healthy ones. There was no significant difference between acute and symptomatic irreversible pulpitis groups. CONCLUSIONS: The results suggest that EphA7 gene may be a marker reflecting inflammatory activity and pain state for human dental pulp.