Anterograde axonal transport of internalized GDNF in sensory and motor neurons

Endogenous glial cell line-derived neurotrophic factor (GDNF) has been shown to be anterogradely transported in sensory and motor neurons which do not express detectable levels of GDNF mRNA. The source of the anterograde axonal GDNF in these neurons has remained unclear. Here we show that radiolabeled GDNF is internalized by dorsal root ganglion (DRG) and hypoglossal motor neurons at their cell bodies and/or their dendrites and that a mechanism exists to transport the internalized GDNF anterogradely in their axons. Since adjacent glial cells express GDNF mRNA, these data support the concept that Schwann cell- or oligodendrocyte-derived GDNF is taken up by DRG and motor neurons, respectively, and transported anterogradely along the axons for release from terminals, resulting in neuronal transcytosis.