Fig. 6. Axon navigation in the retina under NrCAM inhibition. (A-D) Axons growing towards the optic fissure in a retina flat-mount under NrCAM inhibition (top view). (A) Four axons (marked 1-4) grow on pre-existing axons and have large, complex growth cones. Axon 1 forms a growth cone with wide, laterally exploring protrusions (B), detaches from the other axons and turns away at an almost rectangular angle (C). This aberrant growth direction, perpendicular to the pathway to the optic fissure, is maintained for more than 20 minutes (D). Axon 2 turns away from the other axons at a smoother angle (B,C); later it performs a compensatory turn, returning to the correct direction (D). At 54 minutes, axon 3 also starts to deflect (D). Axon 4 grows towards the optic fissure during the observation period, displaying a growth behaviour typically found under control conditions. (E,F) Growth cone kinetic plots of two axons each, growing in retina flat-mounts in control conditions (E) and with NrCAM inhibition (F); each dot represents the position of the growth cone neck localised every two minutes (observation time in brackets). The lower plot in F corresponds to axon 2 shown in A-D. Under control conditions, axons grow rather straight and steadily towards the optic fissure (E). Under NrCAM inhibition the pathway is more crooked and deviating from the correct direction; in addition long pauses and retractions are observed (F). The overall distance covered is considerably shorter under NrCAM inhibition; note that the observation period is about 20% longer in F than in E. Scale bar: 20 µm.