Brain-derived neurotrophic factor differentially regulates retinal ganglion cell dendritic and axonal arborization in vivo.
Expression of the neurotrophin brain-derived neurotrophic factor (BDNF) and its receptor trkB in the ganglion cell layer of the Xenopus retina during retinal ganglion cell (RGC) dendritic arborization indicates that BDNF is spatially and temporally available to influence RGC morphological differentiation (; ). BDNF promotes RGC axon arborization in vivo by acting as a target-derived trophic factor (). To determine whether BDNF also acts locally to regulate RGC dendritic development in vivo, we altered retinal neurotrophin levels at the onset of dendritic arborization and assessed the resulting arbor morphologies of RGCs retrogradely labeled with fluorescent dextrans. Injecting neurotrophins or BDNF function-blocking antibodies coupled to microspheres provided local alterations of retinal neurotrophin levels. BDNF significantly decreased RGC dendritic arbor complexity, whereas neutralizing endogenous BDNF levels with function-blocking antibodies significantly increased dendritic arbor complexity. RGCs exposed to other neurotrophins, as well as RGCs in retinae treated with BDNF but in areas not directly exposed to the neurotrophin, developed dendritic arbors that were indistinguishable from controls, indicating that exogenous BDNF acts specifically and locally. In the tectum, where RGC axons arborize, BDNF had opposite effects. BDNF significantly increased RGC axon arbor complexity and anti-BDNF reduced RGC arborization. Thus, BDNF reduces RGC dendritic arborization within the retina and increases axon arborization in the tectum. These results indicate that BDNF can differentially modulate axonal and dendritic arborization within a single neuronal population in opposing manners and raise the possibility that differential modulation by a neurotrophic factor finely tunes the morphological differentiation program of a neuron.
Lom
B
B
Mental Retardation Research Center, Departments of Psychiatry and Neurobiology, University of California, Los Angeles, Los Angeles, California 90025, USA.
Cohen-Cory
S
S
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001369:Axons / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure*; D019208:Brain-Derived Neurotrophic Factor / Q000276:immunology / Q000494:pharmacology* / Q000502:physiology; D002454:Cell Differentiation; D003712:Dendrites / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure*; D004625:Embryo, Nonmammalian / Q000502:physiology; D005260:Female; D009414:Nerve Growth Factors / Q000494:pharmacology*; D020933:Neurotrophin 3 / Q000494:pharmacology; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure*; D014982:Xenopus laevis / Q000196:embryology
D000906:Antibodies; D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; C073922:neurotrophin 4