Anterograde axonal transport of neurotrophins has been demonstrated recently, but to date such transport has only been shown for brain-derived neurotrophic factor and no other endogenous neurotrophin. Endogenous neurotrophin-3 (NT-3) protein is present in the ganglion cell layer of the chicken retina, as well as the superficial layers of the optic tectum. NT-3 immunolabel in these tectal layers is largely reduced or abolished after treatment of the eye with colchicine or monensin, demonstrating that endogenous NT-3 is transported to the optic tectum by retinal ganglion cells (RGCs). Reverse transcription-PCR analysis of RGCs purified to 100% shows that RGCs, but not tectal cells, express NT-3 mRNA. Blockade of the intercellular transfer of NT-3 within the retina does not reduce the anterograde transport of endogenous NT-3 to the tectum, indicating that a major fraction of the anterogradely transported NT-3 is produced by RGCs rather than taken up from other retinal cells. Immunolabel for the neurotrophin receptor p75, but not trkB or trkC, in the superficial tectum coincides with the NT-3 label. The p75 label in the neuropil of superficial tectal layers is largely reduced or eliminated by injection of monensin in the eye, indicating that p75 protein is exported along RGC axons to the retinotectal terminals and may act as a neurotrophin carrier. These results show that NT-3 is produced by RGCs and that some of this NT-3 is transported anterogradely along the axons to the superficial layers of the tectum, possibly to regulate the survival, synapse formation, or dendritic growth of tectal neurons.
Key words: anterograde transport; NT-3; BDNF; retina; optic tectum; p75 neurotrophin receptor; neurotrophic factor; visual system; RT-PCRNeurotrophins are well known as target-derived, retrograde survival-promoting molecules that require the transport of the neurotrophic factor from the axon terminus to the cell body (Hendry et al., 1974;Johnson et al., 1978;Purves, 1988;Barde, 1989;Oppenheim, 1996). Neurotrophins are also important regulators of neuronal differentiation and synaptic plasticity (Snider, 1994;Thoenen, 1995). Recent studies have shown that neurotrophins can be transported anterogradely along axons (von Bartheld et al., 1996a;Z hou and Rush, 1996;Altar et al., 1997;Conner et al., , 1998Heymach and Barres, 1997;Johnson et al., 1997;Michael et al., 1997;Smith et al., 1997;Yan et al., 1997;Altar and DiStefano, 1998). Such anterograde transport may f unction to provide trophic support from afferents (Linden, 1994;von Bartheld et al., 1996a;Altar et al., 1997), to mediate fast, local effects at synaptic sites (L ohof et al., 1993;Kang and Schuman, 1995;Thoenen, 1995;Berninger and Poo, 1996), or to regulate dendritic growth, neuronal cytoarchitecture, and phenotypes (Purves, 1988;Altar et al., 1997;McAllister et al., 1999). Brainderived neurotrophic factor (BDNF) is stored in axon terminals Fawcett et al., 1997;Michael et al., 1997) and may be released into the synaptic cleft to activate postsynaptic neurotrophin ...