Multiple EPHB receptors contribute directly to dendritic spine development and morphogenesis. These are more broadly involved in post-synaptic development through activation of focal adhesion kinase (FAK) and Rho family GTPases and their GEFs. Dendritic spine morphogenesis is a vital part of the process of synapse formation and maturation during CNS development. Dendritic spine morphogenesis is characterized by filopodia shortening followed by the formation of mature mushroom-shaped spines (Moeller et al. 2006). EPHBs control neuronal morphology and motility by modulation of the actin cytoskeleton. EPHBs control dendritic filopodia motility, enabling synapse formation. EPHBs exert these effects through interacting with the guanine exchange factors (GEFs) such as intersectin and kalirin. The intersectin-CDC42-WASP-actin and kalirin-RAC-PAK-actin pathways have been proposed to regulate the EPHB receptor mediated morphogenesis and maturation of dendritic spines in cultured hippocampal and cortical neurons (Irie & Yamaguchi 2002, Penzes et al. 2003). EPHBs are also involved in the regulation of dendritic spine morphology through FAK which activates the RHOA-ROCK-LIMK-1 pathway to suppress cofilin activity and inhibit cofilin-mediated dendritic spine remodeling (Shi et al. 2009).