Fig. 6
Loss of Gef26 induces motor dysfunction and progressive brain neurodegeneration in the adult fly. a and b Adult locomotor activity is impaired by neuron-specific Gef26 knockdown. a Distribution of the distance climbed by 20-day-old C155-GAL4/+ and C155-GAL4/+; UAS-gef26 RNAi/+ flies over a 30 s period. b Quantification of average climbing distance. c and d Neuron-specific Gef26 knockdown causes brain neurodegeneration in an age-dependent manner. c Frontal brain sections (5 μm) stained with H&E are shown for C155-GAL4/+ and C155-GAL4/+; UAS-gef26 RNAi/+ flies at 2 or 20 days of age. Note the presence of numerous vacuoles (arrowheads) in the brain of 20-day-old C155-GAL4/+; UAS-gef26 RNAi/+ flies. Scale bar, 20 μm. d Quantification of vacuoles with a diameter greater than 5 μm in C155-GAL4/+ and C155-GAL4/+; UAS-gef26 RNAi/+ brains at different ages. n > 10. e Confocal sections of 20-day-old C155-GAL4/+ and C155-GAL4/+; UAS-gef26 RNAi/+ brains stained with anti-caspase-3 (green), anti-Elav (red), and anti-Repo (blue). Anti-caspase-3 signals overlaps with the neuronal cell marker anti-Elav (arrowheads) but not with the glial cell marker anti-Repo. Scale bar, 20 μm. f Quantification of brain vacuolization in 20-day-old wild-type (n = 5), gef26 6/+ (n = 5), rap1 M/+ (n = 6), gef26 6/+; rap1 M/+ (n = 5), dad J1E4/+ (n = 5), and gef26 6/+; dad J1E4/+ (n = 6) flies. g Model for Gef26/Rap1 regulation of BMP-dependent synaptic growth and neuronal survival