EphA4 vs EphA3: fight for the ephrin-As

FIORE L.; DI NAPOLI J.; BENITEZ R.; RAPACIOLI M.; CARRI N.; SCICOLONE G.

Huerta Grande, Córdoba

Congreso; XXVI Congreso Anual de la Sociedad Argentina de Investigación en Neurociencia.; 2011

Sociedad Argentina de Investigación en Neurociencia

Eph/ephrin guide retinal ganglion cells (RCG). Ephrin-As of the caudal tectum repel temporal (T) axons by activating EphAs. We demonstrated that EphA3 stimulates nasal (N) RGCs axon growth to caudal tectum and inhibits branching rostrally to their target area. Our aim was to study the molecular way of action mediated by EphA3. We used retinal explants from chicken embryos treated with EphA3Fc/Fc or PIPLC or KYL (inhibits EphA4 activation ephrin-A mediated). We performed immunocytochemistry, immunoprecipitation and Western blot. NRGCs present higher levels of ephrin-As and EphA4ptyr602. Ephrin-As and EphA4 coexpress (maximum level in NRGCs). As TRGCs -Fc treatment- grow longer axons and present less filopodia and NRGCs present the higher respond to EphA3Fc suggested that ephrin-As-mediated EphA4 forward signaling decreases axon growth and stimulates branching whereas the opposite effects -EphA3Fc treatment- are mediated by decreasing EphA4 forward signaling throughout competition of EphAs binding to ephrin-As. We showed that removing axonal ephrin-As or inhibition EphA4 activation reproduces the effects of EphA3.These results support a novel mechanism of action of EphA3 whereby plays their roles by diminishing the ephrin-As-mediated EphA4 forward signaling. Supported by UBA-CONICET.