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Abstract:

Background: Retinotopic projection onto the tectum/colliculus constitutes the most studied model of topographic mapping and Eph receptors and their ligands, the ephrins, are the best characterized molecular system involved in this process. Ephrin-As, expressed in an increasing rostro-caudal gradient in the tectum/colliculus, repel temporal retinal ganglion cell (RGC) axons from the caudal tectum and inhibit their branching posterior to their termination zones. However, there are conflicting data regarding the nature of the second force that guides nasal axons to invade and branch only in the caudal tectum/colliculus. The predominant model postulates that this second force is produced by a decreasing rostro-caudal gradient of EphA7 which repels nasal optic fibers and prevents their branching in the rostral tectum/colliculus. However, as optic fibers invade the tectum/colliculus growing throughout this gradient, this model cannot explain how the axons grow throughout this repellent molecule. Methodology/Principal Findings: By using chicken retinal cultures we showed that EphA3 ectodomain stimulates nasal RGC axon growth in a concentration dependent way. Moreover, we showed that nasal axons choose growing on EphA3-expressing cells and that EphA3 diminishes the density of interstitial filopodia in nasal RGC axons. Accordingly, in vivo EphA3 ectodomain misexpression directs nasal optic fibers toward the caudal tectum preventing their branching in the rostral tectum. Conclusions: We demonstrated in vitro and in vivo that EphA3 ectodomain (which is expressed in a decreasing rostro-caudal gradient in the tectum) is necessary for topographic mapping by stimulating the nasal axon growth toward the caudal tectum and inhibiting their branching in the rostral tectum. Furthermore, the ability of EphA3 of stimulating axon growth allows understanding how optic fibers invade the tectum growing throughout this molecular gradient. Therefore, opposing tectal gradients of repellent ephrin-As and of axon growth stimulating EphA3 complement each other to map optic fibers along the rostro-caudal tectal axis. © 2012 Ortalli et al.

Registro:

Documento: Artículo
Título:EphA3 expressed in the chicken tectum stimulates Nasal retinal ganglion cell axon growth and is required for retinotectal topographic map formation
Autor:Ortalli, A.L.; Fiore, L.; Di Napoli, J.; Rapacioli, M.; Salierno, M.; Etchenique, R.; Flores, V.; Sanchez, V.; Carri, N.G.; Scicolone, G.
Filiación:Laboratory of Developmental Neurobiology, Institute of Cell Biology and Neurosciences Prof. E. De Robertis (UBA-CONICET), School of Medicine, University of Buenos Aires, Buenos Aires, Argentina
Institute of Multidisciplinary Cell Biology (CONICET-CIC), La Plata, Argentina
Interdisciplinary Group in Theoretical Biology, Department of Bioestructural Sciences, Favaloro University, Buenos Aires, Argentina
Department of Inorganic, Analytical and Physical Chemistry (INQUIMAE), Faculty of Exact and Natural Sciences, University of Buenos Aires, Buenos Aires, Argentina
Palabras clave:ephrin receptor A3; animal cell; animal cell culture; animal tissue; article; cell stimulation; chicken; concentration response; controlled study; embryo; filopodium; human; human cell; in vitro study; in vivo study; nasal retina ganglion cell; nerve fiber growth; nonhuman; nose; optic nerve fiber; optic tectum; protein expression; protein function; protein localization; retina ganglion cell; retinotectal projection; tissue distribution; Animals; Axons; Blotting, Western; Cells, Cultured; Chick Embryo; Chickens; Green Fluorescent Proteins; HEK293 Cells; Humans; Immunohistochemistry; Microscopy, Confocal; Phosphorylation; Receptor, EphA3; Retina; Retinal Ganglion Cells; Superior Colliculi; Tectum Mesencephali; Time Factors; Time-Lapse Imaging; Tissue Culture Techniques; Tyrosine; Visual Pathways
Año:2012
Volumen:7
Número:6
DOI: http://dx.doi.org/10.1371/journal.pone.0038566
Título revista:PLoS ONE
Título revista abreviado:PLoS ONE
ISSN:19326203
CAS:Green Fluorescent Proteins, 147336-22-9; Receptor, EphA3, 2.7.10.1; Tyrosine, 55520-40-6
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19326203_v7_n6_p_Ortalli

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Citas:

---------- APA ----------
Ortalli, A.L., Fiore, L., Di Napoli, J., Rapacioli, M., Salierno, M., Etchenique, R., Flores, V.,..., Scicolone, G. (2012) . EphA3 expressed in the chicken tectum stimulates Nasal retinal ganglion cell axon growth and is required for retinotectal topographic map formation. PLoS ONE, 7(6).
http://dx.doi.org/10.1371/journal.pone.0038566
---------- CHICAGO ----------
Ortalli, A.L., Fiore, L., Di Napoli, J., Rapacioli, M., Salierno, M., Etchenique, R., et al. "EphA3 expressed in the chicken tectum stimulates Nasal retinal ganglion cell axon growth and is required for retinotectal topographic map formation" . PLoS ONE 7, no. 6 (2012).
http://dx.doi.org/10.1371/journal.pone.0038566
---------- MLA ----------
Ortalli, A.L., Fiore, L., Di Napoli, J., Rapacioli, M., Salierno, M., Etchenique, R., et al. "EphA3 expressed in the chicken tectum stimulates Nasal retinal ganglion cell axon growth and is required for retinotectal topographic map formation" . PLoS ONE, vol. 7, no. 6, 2012.
http://dx.doi.org/10.1371/journal.pone.0038566
---------- VANCOUVER ----------
Ortalli, A.L., Fiore, L., Di Napoli, J., Rapacioli, M., Salierno, M., Etchenique, R., et al. EphA3 expressed in the chicken tectum stimulates Nasal retinal ganglion cell axon growth and is required for retinotectal topographic map formation. PLoS ONE. 2012;7(6).
http://dx.doi.org/10.1371/journal.pone.0038566