Pro-neurotrophins Secreted from Retinal Ganglion Cell Axons Are Necessary for EphrinA-p75NTR-mediated Axon Guidance

Overview

Journal Neural Dev

Publisher Biomed Central

Specialty Neurology

Date 2010 Nov 4

PMID 21044296

Citations 28

Authors

Katharine J M Marler

Subathra Poopalasundaram

Emma R Broom

Corinna Wentzel

Uwe Drescher

Affiliations

Soon will be listed here.

Abstract

Background: 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, p75NTR and TrkB, were recently proposed.

Results: 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 p75NTR, abolish repellent ephrinA reverse signalling in the stripe assay.

Conclusions: This indicates that retinal cells secrete proneurotrophins, inducing the ephrinA-p75NTR 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.

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