Tectal EphA3 guides nasal retinal ganglion cells axons during retinotectal mapping by competing with axonal EphA4 for axonal ephrin-As binding

FIORE, LUCIANO; MEDORI, MARA; DI SIERVI, NICOLÁS; ANTÓN, LISANDRO; TERUEL, LUISA; RAPACIOLI, MELINA; SANCHEZ, VIVIANA; CARRI, NÉSTOR GABRIEL; SCICOLONE, GABRIEL

Montreal

Congreso; Canadian Neuroscience Meeting 2014; 2014

Canadian Association for Neuroscience

Tectal EphA3 guides nasal retinal ganglion cells axons during retinotectal mapping by competing with axonal EphA4 for axonal ephrin-As binding. - Poster ID: 92173 Text: 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. Now we postulated that activation of axonal EphA4 decreases axon growth and tectal EphA3 increases axon growth by reducing EphA4 activation throughout competing with axonal EphA4 for axonal ephrin-As binding. We used retinal explants treated with EphA3, PIPLC (sheds ephrin-As) or KYL (EphA4 inhibitor). We electroporated retinas in vivo/in vitro with EphA4, KiEphA4 (dominant negative) or GFP. We showed that: -Nasal RGC axons present higher levels of ephrin-As, colocalization of ephrin-A2/EphA4, and EphA4P than temporal RGC axons. -Axonal response to EphA3 is associated to ephrin-A expression and EphA4-P. -The EphA3 and ephrin-A shedding both decrease the degree of EphA4-P. -Removal of axonal ephrin-As and inhibition of ephrin-As- mediated EphA4 signaling recapitulate the effects of EphA3 on RGC axon growth and branching. -In vitro overexpression of EphA4 produces neurons with shorter axons whereas neurons expressing KiEphA4 have longer axons than the control. In vivo overexpression of EphA4 produces nasal RGC axons with terminal zones closer to the rostral tectum than the control. Nasal RCGs expressing KiEphA4 form terminal zones closer to the caudal tectum. These results support the idea of a new molecular mechanism whereby tectal EphA3 increases axon growth toward the caudal tectum and collaborate to inhibit axon branching in the rostral tectum by decreasing ephrin-As-mediated EphA4 forward signaling.