Double role of EphA3 in retinal axon guidance.

SCICOLONE G.

Los Cocos, Cordoba.

Congreso; XXI Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias (SAN).; 2006

Sociedad Argentina de Investigación en Neurociencias (SAN).

Conferencia: Double role of EphA3 in retinal axon guidance. Gabriel Scicolone. Institute of Cell Biology and Neuroscience. Medicine School. UBA. The retinotectal system is useful to study topographic map formation because nasal retinal ganglion cells (RGC) connect to the caudal tectum and temporal ones connect to the rostral tectum. Eph receptor tyrosine kinases and their ligands, the ephrins, are expressed in complementary gradients in both the retina and the tectum and help guide retinotectal projections. Ephrin-As located in the caudal tectum repel temporal axons activating their EphA3 receptors. However, it is not known whether EphA3 expressed in the rostral tectum also participates in axon guidance. Therefore, we investigated the effects of the EphA3 extracellular domain (fused to Fc or transfected in 293 cells) on RGC neurite outgrowth. We used dissociated retinal neurons and retinal explants prepared from chicken embryos at 6 days of development. EphA3 ectodomain (that is expressed in temporal retina) increases cell adhesion and neuritogenesis of temporal RGC suggesting that EphA3 could favor retinal compartmentalization and neuritogenesis. Both nasal and temporal axons grow longer on EphA3Fc in a concentration dependent way. In time-lapse experiments we showed that the majority of growth cones expand when contacting 293 cells transfected with EphA3 but not control cells. The majority of nasal growth cones extend on cells expressing EphA3 while the majority of temporal ones adhere without extending. This behavior is similar to that observed on the tectal surface. While EphA3 could influence nasal retinal axons by binding to ephrin-As, the EphA3 target on temporal growth cones is unknown. We showed that temporal growth cones express ephrin-A6 and in vitro experiments shedding axonal ephrin-As suggest that these molecules mediate the stimulatory effect of EphA3 ectodomain. These results support our hypothesis that tectal EphA3 stimulate axonal growth toward whereas tectal ephrin-As repel axons from the caudal tectum and the differential response of nasal and temporal RGC would be mediated by the different concentrations of axonal EphAs and ephrin-As acting as receptors. This work was supported by grants from CONICET and UBA