Figure 8.

Tau knockdown reduces axon outgrowth, which is rescued with human tau Fluorescence images of fixed cultured cortical neurons (A) nucleofected with a control GFP-vector, hamster tau shRNA, hamster tau shRNA coexpressed with a single human tau isoform and hamster tau shRNA coexpressed with all 3R human tau isoforms. Neurons were nucleofected, replated, and allowed to extend axons for 24 h. Fixed cultures were labeled with antibodies to tubulin to show cortical axons. The arrow indicates a neuron that contains both the hamster shRNA tau knockdown construct and all 3R human tau isoforms. This neuron has an axon similar in length to a wild-type neuron in close proximity. The arrowhead indicates a neuron containing only the knockdown construct and has very little neurite outgrowth. As shown in the histograms (B), tau knockdown reduced axon length by ∼30%. Rescue with a single 3Rtau isoform only partially rescued axon outgrowth whereas all three human 3R tau isoforms restored axons to control lengths. *p < 0.05, ****p < 0.0001. Scale bar, 50 μm.