Eph receptor tyrosine kinases family and their ligands, ephrins, are membrane proteins that primarily regulate cell to cell repulsion and cell adhesion and movement by modulating the organization of the actin cytoskeleton mainly through Rho family GTPases. Eph receptors and ephrin ligand signaling regulaes many aspects of cell interaction in the developing neocortex, including migration and axonal target recognition. Ephrin signaling plays an important role in guiding neurons and their projections during embryonic development^1,2_.

In mammals, the Eph receptor tyrosine kinases family has 14 members that are divided into 2 subclasses, the EphA (A1–A8 and A10) and EphB (B1–B4 and B6). This division is based on the sequence similarity of their extracellular domains. EphA receptors bind to glycosylphosphatidyl inositol-anchored ephrin-A ligands, and EphB receptors bind to transmembrane ephrin-B proteins_.                                                              

The ephrin-A proteins include five members ephrin-A1 to ephrin-A5 whereas ephrin-B proteins include three ephrin-B1 to ephrin-B3^2,3.

Ephrin-A2 protein is abundantly expressed in retinal axons. Mutations in Ephrin-A2 disrupts topographic ordering of projections in the developing visual system. A knockout of ephrin-A2 in adult mice shows focal patches of disorganized neocortical laminar architecture, ranging in severity from reduced neuronal density to a complete lack of neurons^1,2.