Opposing roles for neurotrophin-3 in targeting and collateral formation of distinct sets of developing cortical neurons.
Neurotrophin-3 and its receptor TrkC are expressed during the development of the mammalian cerebral cortex. To examine whether neurotrophin-3 might play a role in the elaboration of layer-specific cortical circuits, slices of layer 6 and layers 2/3 neurons were cultured in the presence of exogenously applied neurotrophin-3. Results indicate that neurotrophin-3 promotes axonal branching of layer 6 axons, which target neurotrophin-3-expressing layers in vivo, and that it inhibits branching of layers 2/3 axons, which avoid neurotrophin-3-expressing layers. Such opposing effects of neurotrophin-3 on axonal branching were also observed with embryonic cortical neurons, indicating that the response to neurotrophin-3 is specified at early developmental stages, prior to cell migration. In addition to its effects on fiber branching, axonal guidance assays also indicate that neurotrophin-3 is an attractive signal for layer 6 axons and a repellent guidance cue for layers 2/3 axons. Experiments with specific antibodies to neutralize neurotrophin-3 in cortical membranes revealed that endogenous levels of neurotrophin-3 are sufficient to regulate branching and targeting of cortical axons. These opposing effects of neurotrophin-3 on specific populations of axons demonstrate that it could serve as one of the signals for the elaboration of local cortical circuits.
INSERM Unité 371 'Cerveau et Vision' 18, Avenue du Doyen Lépine, France.
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Castellani
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Bolz
D000818:Animals; D001369:Axons / Q000648:ultrastructure; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology / Q000254:growth & development*; D046508:Culture Techniques; D009414:Nerve Growth Factors / Q000037:antagonists & inhibitors / Q000502:physiology*; D009474:Neurons / Q000166:cytology; D020933:Neurotrophin 3; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology; D020812:Receptor, trkC; D017475:Receptors, Nerve Growth Factor / Q000502:physiology; D015398:Signal Transduction
D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D017475:Receptors, Nerve Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D020812:Receptor, trkC