Pro-neurotrophins secreted from retinal ganglion cell axons are necessary for ephrinA-p75<sup>NTR</sup>-mediated axon guidance

<p>Abstract</p> <p>Background</p> <p>Retinotectal map formation develops via topographically specific guidance and branching of retinal axons in their target area. This process is controlled, in part, by reverse signalling of ephrinAs expressed on retinal axons. As glyc...

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Main Authors: Broom Emma R, Poopalasundaram Subathra, Marler Katharine JM, Wentzel Corinna, Drescher Uwe
Format: Article
Language:English
Published: BMC 2010-11-01
Series:Neural Development
Online Access:http://www.neuraldevelopment.com/content/5/1/30
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author Broom Emma R
Poopalasundaram Subathra
Marler Katharine JM
Wentzel Corinna
Drescher Uwe
author_facet Broom Emma R
Poopalasundaram Subathra
Marler Katharine JM
Wentzel Corinna
Drescher Uwe
author_sort Broom Emma R
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>Retinotectal map formation develops via topographically specific guidance and branching of retinal axons in their target area. This process is controlled, in part, by reverse signalling of ephrinAs expressed on retinal axons. As glycosylphosphatidylinositol-anchored molecules, ephrinAs require transmembrane co-receptors to exert this function, for which the two neurotrophin receptors, p75<sup>NTR </sup>and TrkB, were recently proposed.</p> <p>Results</p> <p>We show here that the ligands for these receptors, the brain-derived neurotrophic factor precursor (proBDNF) and its processed form, BDNF, respectively, control the branching of retinal axons antagonistically, which they mediate by inducing the corresponding neurotrophin receptor-ephrinA complexes. Moreover, scavenging proneurotrophins, by adding antibodies specific for the pro-domain of proBNDF or a soluble extracellular domain of p75<sup>NTR</sup>, abolish repellent ephrinA reverse signalling in the stripe assay.</p> <p>Conclusions</p> <p>This indicates that retinal cells secrete proneurotrophins, inducing the ephrinA-p75<sup>NTR </sup>interaction and enabling repellent axon guidance. The antagonistic functions of proBDNF and BDNF raise the possibility that topographic branching is controlled by local control of processing of proneurotrophins.</p>
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spelling doaj.art-50b63152d2874762adb1aba790cfc2e02022-12-21T22:40:09ZengBMCNeural Development1749-81042010-11-01513010.1186/1749-8104-5-30Pro-neurotrophins secreted from retinal ganglion cell axons are necessary for ephrinA-p75<sup>NTR</sup>-mediated axon guidanceBroom Emma RPoopalasundaram SubathraMarler Katharine JMWentzel CorinnaDrescher Uwe<p>Abstract</p> <p>Background</p> <p>Retinotectal map formation develops via topographically specific guidance and branching of retinal axons in their target area. This process is controlled, in part, by reverse signalling of ephrinAs expressed on retinal axons. As glycosylphosphatidylinositol-anchored molecules, ephrinAs require transmembrane co-receptors to exert this function, for which the two neurotrophin receptors, p75<sup>NTR </sup>and TrkB, were recently proposed.</p> <p>Results</p> <p>We show here that the ligands for these receptors, the brain-derived neurotrophic factor precursor (proBDNF) and its processed form, BDNF, respectively, control the branching of retinal axons antagonistically, which they mediate by inducing the corresponding neurotrophin receptor-ephrinA complexes. Moreover, scavenging proneurotrophins, by adding antibodies specific for the pro-domain of proBNDF or a soluble extracellular domain of p75<sup>NTR</sup>, abolish repellent ephrinA reverse signalling in the stripe assay.</p> <p>Conclusions</p> <p>This indicates that retinal cells secrete proneurotrophins, inducing the ephrinA-p75<sup>NTR </sup>interaction and enabling repellent axon guidance. The antagonistic functions of proBDNF and BDNF raise the possibility that topographic branching is controlled by local control of processing of proneurotrophins.</p>http://www.neuraldevelopment.com/content/5/1/30
spellingShingle Broom Emma R
Poopalasundaram Subathra
Marler Katharine JM
Wentzel Corinna
Drescher Uwe
Pro-neurotrophins secreted from retinal ganglion cell axons are necessary for ephrinA-p75<sup>NTR</sup>-mediated axon guidance
Neural Development
title Pro-neurotrophins secreted from retinal ganglion cell axons are necessary for ephrinA-p75<sup>NTR</sup>-mediated axon guidance
title_full Pro-neurotrophins secreted from retinal ganglion cell axons are necessary for ephrinA-p75<sup>NTR</sup>-mediated axon guidance
title_fullStr Pro-neurotrophins secreted from retinal ganglion cell axons are necessary for ephrinA-p75<sup>NTR</sup>-mediated axon guidance
title_full_unstemmed Pro-neurotrophins secreted from retinal ganglion cell axons are necessary for ephrinA-p75<sup>NTR</sup>-mediated axon guidance
title_short Pro-neurotrophins secreted from retinal ganglion cell axons are necessary for ephrinA-p75<sup>NTR</sup>-mediated axon guidance
title_sort pro neurotrophins secreted from retinal ganglion cell axons are necessary for ephrina p75 sup ntr sup mediated axon guidance
url http://www.neuraldevelopment.com/content/5/1/30
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AT poopalasundaramsubathra proneurotrophinssecretedfromretinalganglioncellaxonsarenecessaryforephrinap75supntrsupmediatedaxonguidance
AT marlerkatharinejm proneurotrophinssecretedfromretinalganglioncellaxonsarenecessaryforephrinap75supntrsupmediatedaxonguidance
AT wentzelcorinna proneurotrophinssecretedfromretinalganglioncellaxonsarenecessaryforephrinap75supntrsupmediatedaxonguidance
AT drescheruwe proneurotrophinssecretedfromretinalganglioncellaxonsarenecessaryforephrinap75supntrsupmediatedaxonguidance