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.
Castellani
V
V
INSERM Unité 371 'Cerveau et Vision' 18, Avenue du Doyen Lépine, France.
Bolz
J
J
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