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EphA3 expressed in the chicken tectum stimulates nasal retinal ganglion cell axon growth and is required for retinotectal topographic map formation.

Ortalli AL, Fiore L, Di Napoli J, Rapacioli M, Salierno M, Etchenique R, Flores V, Sanchez V, Carri NG, Scicolone G - PLoS ONE (2012)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: 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.

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.

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General models to account for topographic mapping along the rostro-caudal axis of the retinotectal/collicular system.In both models (A and B) opposing gradients of ephrin-As and EphAs establish the local addresses in the tectum/colliculus whereas opposing gradients of ephrin-As and EphAs establish the relative sensitivity of axons according to the RGC bodies location. Tectal/collicular ephrin-As inhibit temporal RGCs axon growth and termination zone formation. (A) In this model collicular EphA7 or EphA8 repel nasal RGC axon growth and inhibit termination zone formation. Repellent effect of EphAs on axon growth would prevent RGC axons from invading the colliculus. (B) In our model tectal EphA3 stimulates nasal RGCs axon growth and inhibits termination zone formation. This allows us to explain how RGC axons invade the tectum. Optic fibers (OF), Optic tectum (OT), superior colliculus (SC).
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pone-0038566-g008: General models to account for topographic mapping along the rostro-caudal axis of the retinotectal/collicular system.In both models (A and B) opposing gradients of ephrin-As and EphAs establish the local addresses in the tectum/colliculus whereas opposing gradients of ephrin-As and EphAs establish the relative sensitivity of axons according to the RGC bodies location. Tectal/collicular ephrin-As inhibit temporal RGCs axon growth and termination zone formation. (A) In this model collicular EphA7 or EphA8 repel nasal RGC axon growth and inhibit termination zone formation. Repellent effect of EphAs on axon growth would prevent RGC axons from invading the colliculus. (B) In our model tectal EphA3 stimulates nasal RGCs axon growth and inhibits termination zone formation. This allows us to explain how RGC axons invade the tectum. Optic fibers (OF), Optic tectum (OT), superior colliculus (SC).

Mentions: The question about the effect of the second tectal/collicular gradient on RGC axon growth (stimulation versus repulsion) implies fundamental consequences on the way the optic fibers invade the tectum/colliculus. As optic fibers invade the tectum/colliculus throughout the area where the highest concentration of EphAs are expressed, the repellent effect of EphA7 would prevent optic fibers from invading the target (Fig. 8A). However, the existence of a molecular gradient of EphA3, which stimulates axon growth throughout it, can explain how the optic fibers invade the tectum/colliculus [1] (Fig. 8B).


EphA3 expressed in the chicken tectum stimulates nasal retinal ganglion cell axon growth and is required for retinotectal topographic map formation.

Ortalli AL, Fiore L, Di Napoli J, Rapacioli M, Salierno M, Etchenique R, Flores V, Sanchez V, Carri NG, Scicolone G - PLoS ONE (2012)

General models to account for topographic mapping along the rostro-caudal axis of the retinotectal/collicular system.In both models (A and B) opposing gradients of ephrin-As and EphAs establish the local addresses in the tectum/colliculus whereas opposing gradients of ephrin-As and EphAs establish the relative sensitivity of axons according to the RGC bodies location. Tectal/collicular ephrin-As inhibit temporal RGCs axon growth and termination zone formation. (A) In this model collicular EphA7 or EphA8 repel nasal RGC axon growth and inhibit termination zone formation. Repellent effect of EphAs on axon growth would prevent RGC axons from invading the colliculus. (B) In our model tectal EphA3 stimulates nasal RGCs axon growth and inhibits termination zone formation. This allows us to explain how RGC axons invade the tectum. Optic fibers (OF), Optic tectum (OT), superior colliculus (SC).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3369860&req=5

pone-0038566-g008: General models to account for topographic mapping along the rostro-caudal axis of the retinotectal/collicular system.In both models (A and B) opposing gradients of ephrin-As and EphAs establish the local addresses in the tectum/colliculus whereas opposing gradients of ephrin-As and EphAs establish the relative sensitivity of axons according to the RGC bodies location. Tectal/collicular ephrin-As inhibit temporal RGCs axon growth and termination zone formation. (A) In this model collicular EphA7 or EphA8 repel nasal RGC axon growth and inhibit termination zone formation. Repellent effect of EphAs on axon growth would prevent RGC axons from invading the colliculus. (B) In our model tectal EphA3 stimulates nasal RGCs axon growth and inhibits termination zone formation. This allows us to explain how RGC axons invade the tectum. Optic fibers (OF), Optic tectum (OT), superior colliculus (SC).
Mentions: The question about the effect of the second tectal/collicular gradient on RGC axon growth (stimulation versus repulsion) implies fundamental consequences on the way the optic fibers invade the tectum/colliculus. As optic fibers invade the tectum/colliculus throughout the area where the highest concentration of EphAs are expressed, the repellent effect of EphA7 would prevent optic fibers from invading the target (Fig. 8A). However, the existence of a molecular gradient of EphA3, which stimulates axon growth throughout it, can explain how the optic fibers invade the tectum/colliculus [1] (Fig. 8B).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: 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.

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.

Show MeSH
Related in: MedlinePlus