Nurr1 co-localizes with EphB1 receptors in the developing ventral midbrain, and its expression is enhanced by the EphB1 ligand, ephrinB2

Both ephrins and the transcription factor, Nurr1, are critically involved in CNS development and, particularly, in the ontogenesis of the nigro-striatal system. Here we examined whether the ephrin receptor, EphB1, and Nurr1 share a similar expression pattern in the embryonic brain and whether expression of Nurr1 is under the control of EphB1 activation. The transcripts of EphB1 receptor and Nurr1 showed a similar pattern of expression in the ventral midbrain of mice at early stages of embryonic development (E11.5 and E12.5). At later stages (E15.5), only Nurr1 mRNA could still be detected in significant amounts in the A9-A10 regions of the ventral midbrain, whereas the two transcripts still showed a similar pattern of expression in discrete regions of the hindbrain. To examine whether activation of EphB1 receptor could induce the expression of Nurr1 in the ventral midbrain, we applied the EphB1 ligand, ephrinB2, to explants of embryonic mouse ventral midbrain. Low concentrations of clustered ephrinB2 (0.25 mug/mL) enhanced Nurr1 mRNA and protein levels, whereas higher concentrations were inactive. We conclude that activation of EphB1 receptors by appropriate concentrations of its ligand ephrinB2 might contribute to the acquisition of a dopaminergic fate in developing midbrain ventral neurones.