.- EphA3 Expressed in the Chicken Tectum Stimulates Nasal Retinal Ganglion Cell Axon Growth and Is Required for Retinotectal Topographic Map Formation.

ORTALLI AL* (*)(*) EQUALLY CONTRIBUTING AUTHOR; FIORE L.* ; DI NAPOLI J.; RAPACIOLI M.; SALIERNO M.; ETCHENIQUE M.; FLORES V.; SANCHEZ V.; CARRI N.; SCICOLONE G.

PLOS ONE

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2012 p. 1 - 17

1932-6203

Background: Retinotopic projection onto the tectum/colliculus constitutes the moststudied model of topographic mapping and Eph receptors and their ligands, theephrins, are the best characterized molecular system involved in this process. Ephrin-As, expressed in an increasing rostro-caudal gradient in the tectum/colliculus, repeltemporal retinal ganglion cell (RGC) axons from the caudal tectum and inhibit theirbranching posterior to their termination zones. However, there are conflicting dataregarding the nature of the second force that guides nasal axons to invade and branchonly in the caudal tectum/colliculus. The predominant model postulates that thissecond force is produced by a decreasing rostro-caudal gradient of EphA7 whichrepels nasal optic fibers and prevent them from branching in the rostraltectum/colliculus. However, as optic fibers invade the tectum/colliculus growingthroughout this gradient, this model cannot explain how the axons grow throughout thispostulated repelent molecule.Methodology/Principal findings: By using chicken retinal cultures we showed thatEphA3 ectodomain stimulates nasal RGC axon growth in a concentration dependentway, that nasal axons choose growing on EphA3-expressing cells and that EphA3inhibits interstitial branches formation in nasal RGCs. Accordingly, in vivo EphA3ectodomain misexpression sends nasal optic fibers toward the caudal tectum inhibitingthem from branching.Conclusions: We first demonstrated in vitro and in vivo that EphA3 ectodomain (whichexpresses in a decreasing rostro-caudal gradient in the tectum) is necessary fortopographic mapping by stimulating the nasal axon growth toward the caudal tectumand inhibiting their branching in the rostral tectum. Furthermore, the stimulating axongrowth nature of EphA3 allows to understand how optic fibers invade the tectumgrowing throughout this molecular gradient. Therefore, opposing tectal gradients ofrepellent ephrin-As and axon growth stimulating EphA3 complement each other to mapoptic fibers along the rostro-caudal tectal axis.