IBCN   20355
INSTITUTO DE BIOLOGIA CELULAR Y NEUROCIENCIA "PROFESOR EDUARDO DE ROBERTIS"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
EphA3 ectodomain and GDNF regulate FAK activity during axon growth of retinal ganglion cells. Luisa Renee Teruel, Viviana Sanchez, Luciano Fiore, Gabriel Scicolone .
Autor/es:
MEDORI, MARA; FIORE; LUCIANO; SPELZINI, GONZALO; SANCHEZ, VIVIANA; TERUEL, LUISA R; SCICOLONE, GABRIEL
Lugar:
Daegu
Reunión:
Congreso; The Xth IBRO World Congress of Neuroscience; 2019
Institución organizadora:
IBRO
Resumen:
EphA3 ectodomain and GDNF regulate FAK activity during axon growth of retinal ganglion cells. GONZALO SPELZINI , MARA MEDORI , LUISA RENEE TERUEL , VIVIANA SANCHEZ , LUCIANO FIORE , GABRIEL SCICOLONE CONICET ? Universidad de Buenos Aires, Instituto de Biología Celular y Neurociencias ?Prof. E. De Robertis? (IBCN); Universidad de Buenos Aires, Facultad de Medicina, Departamento de Biología Celular, Histología, Embriología y Genética, Buenos Aires, Argentina The Eph/ephrin system regulates axon guidance during chicken retinotectal mapping. We demonstrated 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 throughout decreasing the EphA4 signaling by competing with EphA4 for ephrin-As binding. Glial cell derived neurotrophic factor (GDNF) stimulates motor neurons axon growth interacting with Eph/ephrin system. The purposes of this work were to study whether EphA3 and GDNF act in a combinatorial way on RGC axon growth and guidance and investigate which molecules participate downstream in these processes. We cultured chicken embryo dissociated retinal neurons and 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, growth cone behavior and axon guidance. Besides, retinal tissue fragments were stimulated as the cultures and the cell lysates were analyzed by Western blot to determine intracellular molecules regulated downstream of EphA3 ectodomain and GDNF. The results showed that: Decreased ephrin-A-mediated EphA4 forward signaling by EphA3-Fc and GDNF increase nasal RGC axon growth and growth cones migration whereas EphA3-Fc has an attractant axon guidance effect. EphA3-Fc plus GDNF increase axon growth and the proportion of advancing growth cones more than EphA3-Fc and GDNF alone. GDNF and EphA3-Fc decrease EphA4-ephrin-A2 on, and both of them modify Focal Adhesion Kinase (FAK) activity. This suggests that EphA3 ectodomain and GDNF potentiate nasal RGC axon growth and that the decrease of ephrin-A- mediated EphA4 signaling could participate in the effects of both of them. Besides, FAK activity participates downstream of EphA3 ectodomain and GDNF-mediated axon growth. Supported by Research Grants: PIP 0441 from CONICET and UBACYT 0526 and 0769.