Regional Differences in the Developing Cerebral Cortex Revealed by Ephrin-A5 Expression

The development of axonal connections between thalamic nuclei and their cortical target areas occurs in a highly specific manner. To explore the mechanisms of thalamocortical axon pathfinding, we investigated the expression of several members of the ephrin and Eph gene families in the forebrain. The Eph ligand ephrin-A5 was expressed in three distinct gradients during the development of the telencephalon. The first gradient occurred in the cortical ventricular zone and established ephrin-A5 as one of the earliest markers distinguishing cells residing in the anterior versus posterior cortical neuroepithelium. The second gradient was apparent in the subplate and occurred in spatial opposition to a distinct gradient for the low-affinity NGF receptor p75. This finding reveals that different regions of the early subplate are molecularly heterogeneous. Third, we confirmed that ephrin-A5 is expressed in a bi-directional gradient in the cortical plate, with highest levels in the somatomotor cortex. Three putative receptors for ephrin-A5 -- EphA3, EphA4 and EphA5 -- showed distinct expression patterns in the developing thalamus. The graded distributions of ephrin-A5 in the developing subplate and cortex and the expression of its receptors in the thalamus are consistent with the notion that the Eph ligands and their receptors may function in the topographic mapping of thalamic axons to specific cortical areas.