EphA3 ectodomain and GDNF regulate axon growth and guidance of retinal ganglion cells.

SPELZINI, GONZALO; SANCHEZ, VIVIANA; CARRI, NÉSTOR GABRIEL; MEDORI, MARA; SCICOLONE, GABRIEL

Córdoba

Congreso; XXXIII CONGRESO ANUAL SAN 2018; 2018

Sociedad Argentina de Investigación en Neurociencias

The Eph/ephrin system participates in the chicken retinotectal mapping. We showed that: Tectal EphA3 stimulates axon growth of nasal retinal ganglion cells (RGC) toward the caudal tectum preventing them from branching in the rostral tectum. Ephrin-A-mediated EphA4 forward signaling decreases axon growth of RGC whereas the tectal EphA3 produces the opposite effects by decreasing the EphA4 signaling by competing with EphA4 for ephrin-As binding. GDNF stimulates motor neurons axon growth binding to GFRalfa, RET functions as correceptor of GFRalfa and binds to ephrin-A5. Thus, RET integrates the effects of GDNF on GFRalfa and of EphA4 through ephrin-A5.Our purpose was to study the individual and combinatorial effects of EphA3 and GDNF on axon growth and guidance. We cultured chicken embryo retinal explants exposed to control conditions, to EphA3 ectodomain (EphA3-Fc), to GDNF or to EphA3-Fc plus GDNF to evaluate their effects on axon growth and guidance using stripe assay.The results showed that: Decreased ephrin-A-mediated EphA4 forward signaling by EphA3-Fc increases nasal RGC axon growth and has an axon guidance effect. GDNF increases RGC axon growth and decreases EphA4-ephrin-A2 colocalization as EphA3-Fc does. EphA3-Fc plus GDNF increase axon growth more than EphA3-Fc and GDNF alone. This suggests that EphA3 and GDNF potentiate nasal RGC axon growth and that decrease of ephrin-A-mediated EphA4 signaling could participate in the effects of both of them.Supported by Research Grants: PIP 0441 from CONICET and UBACYT 0526.