Pro-neurotrophins secreted from retinal ganglion cell axons are necessary for ephrinA-p75NTR-mediated axon guidanceReportar como inadecuado

Pro-neurotrophins secreted from retinal ganglion cell axons are necessary for ephrinA-p75NTR-mediated axon guidance - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Neural Development

, 5:30

First Online: 02 November 2010Received: 30 June 2010Accepted: 02 November 2010


BackgroundRetinotectal 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 and TrkB, were recently proposed.

ResultsWe 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, abolish repellent ephrinA reverse signalling in the stripe assay.

ConclusionsThis indicates that retinal cells secrete proneurotrophins, inducing the ephrinA-p75 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.

AbbreviationsBDNFbrain derived neurotrophic factor

CHOChinese hamster ovary

Eembryonic day

eGFPenhanced green fluorescent protein

NGFnerve growth factor

NTRneurotrophin receptor

RGCretinal ganglion cells

RNAiRNA interference

Trktropomyosin-related kinase.

Electronic supplementary materialThe online version of this article doi:10.1186-1749-8104-5-30 contains supplementary material, which is available to authorized users.

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Autor: Katharine JM Marler - Subathra Poopalasundaram - Emma R Broom - Corinna Wentzel - Uwe Drescher


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