Pro-neurotrophins secreted from retinal ganglion cell axons are necessary for ephrinA-p75NTR-mediated axon guidance.
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.
MRC Centre for Developmental Neurobiology, King's College London, New Hunt's House, Guy's Campus, London SE1 1UL, UK.
Katharine J M
KJ
Marler
Subathra
S
Poopalasundaram
Emma R
ER
Broom
Corinna
C
Wentzel
Uwe
U
Drescher
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001369:Axons / Q000187:drug effects / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000276:immunology / Q000378:metabolism*; D016466:CHO Cells; D002645:Chickens; D006224:Cricetinae; D003412:Cricetulus; D018274:Electroporation / Q000379:methods; D036342:Ephrins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D047468:Immunoprecipitation / Q000379:methods; D008024:Ligands; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins; D009924:Organ Culture Techniques; D011498:Protein Precursors / Q000276:immunology / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*; D012160:Retina; D012165:Retinal Ganglion Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014162:Transfection / Q000379:methods
D000906:Antibodies; D019208:Brain-Derived Neurotrophic Factor; D036342:Ephrins; D008024:Ligands; D008164:Luminescent Proteins; D009419:Nerve Tissue Proteins; D011498:Protein Precursors; D034741:RNA, Small Interfering; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor; C426674:brain-derived neurotrophic factor precursor; C068313:Ngfr protein, rat