Retinal ganglion cells axon growth depends on the grade of EphA4 phosphorylation.

FIORE L; DI NAPOLI J; ALONSO C; RAPACIOLI M; CARRI N.G.; SCICOLONE G

Huerta Grande, Córdoba

Congreso; a II Reunión Conjunta de Neurociencias (XXV Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias-SAN y XII Taller Argentino de Neurociencias -TAN-); 2010

Eph receptor tyrosine kinases and ephrins guide retinal ganglion cells (RGCs) axons in the tectum. Ephrin-As located in the caudal tectum repel temporal (T) axons by activating EphAs. We demonstrated that tectal EphA3 stimulates nasal (N) RGCs axon growth to caudal tectum. It is not known which molecule/s mediates the effect of EphA3. Our objectives were to investigate if 1) the RGCs that express higher levels of ephrin-As grow shorter axons but increase their growth when binding to EphA3; 2) inactivation of axonal EphA4 mimics EphA3 effect on axon growth. We used retinal explants from 7 days-old chicken embryos exposed to Kyl (EphA4 inihibitor) or EphA3-Fc, performed immunocytochemistry against Eph/ephrins-As and Western blot against phosphorylated EphA4. EphA4 is expressed in a shallow decreasing naso to temporal gradient. T RGCs express lower levels of ephrin-As and grow longer axons. N RGCs express higher levels of ephrin-As and grow longer axons with EphA4 inhibition or with EphA3-Fc. EphA3-Fc modifies the profile of EphA4 phosphorylation. This suggests that EphA4 activation by coexpressed ephrin-As decreases axon growth and that EphA4 inhibition stimulates axon growth produced by EphA3. It is postulated that tectal EphA3 might stimulate N RGCs axon growth through binding with axonal ephrin-As and indirectly inhibiting EphA4 activity.