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.

No abstract

The dendritic and axonal arbors of developing retinal ganglion cells (RGCs) are exposed to two sources of BDNF: RGC dendrites are exposed to BDNF locally within the retina, and RGC axons are exposed to BDNF at the target, the optic tectum. Our previous studies demonstrated that increasing tectal BDNF levels promotes RGC axon terminal arborization, whereas increasing retinal BDNF levels inhibits RGC dendritic arborization. These results suggested that differential neurotrophic action at the axon versus dendrite might be responsible for the opposing effects of BDNF on RGC axonal versus dendritic arborization. To explore this possibility, we examined the effects of altering BDNF levels at the optic tectum on the elaboration of RGC dendritic arbors in the retina. Increasing tectal BDNF levels resulted in a significant increase in dendritic branching, whereas neutralizing endogenous tectal BDNF with function-blocking antibodies significantly decreased dendritic arbor complexity. Thus, RGC dendritic arbors react in opposing manners to retinal- versus tectal-derived BDNF. Alterations in retinal BDNF levels, however, did not affect axon terminal arborization. Thus, RGC dendritic arborization is controlled in a complementary manner by both local and target-derived sources of BDNF, whereas axon arborization is modulated solely by neurotrophic interactions at the target. Together, our results indicate that developing RGCs modulate dendritic arborization by integrating signals from discrete sources of BDNF in the eye and brain. Differential integration of spatially discrete neurotrophin signals within a single neuron may therefore finely tune afferent and efferent neuronal connectivity.

No abstract