Inhibition of EphA4 increases axon growth of retinal ganglion cells

OLIVIERI, VANESA; ORTALLI, ANA L; DI NAPOLI, JENNIFER; SALCEDO, MARIANA; PASQUALE, ELENA B; CARRI, NESTOR G; SCICOLONE, GABRIEL

Bucios, Brasil

Congreso; . I Congress IBRO/LARC of Neurosciences for Latin America, Caribbean and Iberian Peninsula; 2008

IBRO/LARC of Neurosciences for Latin America, Caribbean and Iberian Peninsula

Inhibition of  EphA4 increases  axon growth of retinal ganglion cells Vanesa Olivieri1, Ana L Ortalli1, Jennifer Di Napoli1, Mariana Salcedo1, Elena B Pasquale3, Néstor G Carri2, Gabriel Scicolone1. 1. Inst Cell Biol. and Neurosci. Med School, UBA, Bs As, Argentina. 2. Molecular Biology, IMBICE (CIC,CCT-La Plata,CONICET), Argentina. 3. The Burnham Inst, La Jolla, USA. The retinotectal system is useful to study topographic map formation because nasal retinal ganglion cells (RGC) connect to the caudal tectum and temporal ones connect to the rostral tectum. Eph receptor tyrosine kinases and their ligands, the ephrins, are expressed in complementary gradients in both the retina and the tectum and contribute to guide retinotectal projections. Both Ephs and ephrins function as receptors and ligands producing bidirectional signaling. Ephrin-As located in the caudal tectum repel temporal axons by activating the axonal EphA3. Ephrin-As expressed in nasal RGC activate EphA4 converting nasal RGC less sensitive to tectal ephrin-As. We demonstrated that tectal EphA3 promotes axon growth of RGC toward the caudal tectum. Our objective was to investigate whether the level of activation of axonal EphA4 ,produced independently of tectal ephrin-As, regulates the rate of axon growth of RGC. Methods: We used retinal explants from 7 days-old chicken embryos to investigate: 1) the expression pattern of ephrin-As and EphA4 in growth cones in vitro by immunocytochemistry; and 2) the effect of inhibiting the axonal EphA4 activaty by using an inhibitory peptide (KYL) (Molecular and Cel Neurosci. 24:1000, 2003)  in vitro. Results: EphA4 is expressed homogeneously in nasal and temporal growth cones. Ephrin-As are highly expressed in nasal and moderately in temporal growth cones. It was previously demonstrated that axonal ephrin-As activate axonal EphA4. Control temporal RGCs grow statistically significant longer axons than nasal ones. Inhibition of axonal EphA4 produces a significant increase in axon growth of RGC. . Conclusions: The fact that inhibition of axonal EphA4 increases axon growth independently of tectal ephrin-As suggests that activation of axonal EphA4 by axonal ephrin-As decreases axon growth in vitro. This supports the idea that topographic mapping is influenced by Eph-ephrin interactions not only between RGC axons and tectal cells but also among neighboring axons. References: Molecular and Cel Neurosci. 24:1000, 2003 This work was supported by grants from CONICET, UBA