(A) Time lapse imaging of regenerating growth cones of cortical neurons
from Rph3a+/+ (n = 19) and
Rph3a−/− (n = 17), 5–7 days
post axotomy. Cortical neurons were transfected with Life Act-mScarlet to label
F-actin rich filopodial structures. Maximum intensity
z-projection for three time points were shown for each
genotype. Left are raw images used for automatic filopodia detection,
highlighted in purple. Scale bar, 5 μm.
(B) Quantification of filopodial length for 30 min time-lapse, mean
± SEM for individual growth cones from 3 biological replicates. **p =
0.0035 (U = 71), by non-parametrie Mann-Whitney test.
(C) The ratio of filopodial number to the edge length of lamellipodia,
mean ± SEM. *p = 0.0415 (U = 92), by non-parametric Mann-Whitney
test.
(D) The rate of axon extension over 30 min time-lapse window, mean
± SEM. ****p < 0.0001 (U = 0), by non-parametric Mann-Whitney
test.
(E) Area of regenerating growth cones from experiment as in A. *p
< 0.05 (U = 0), by non-parametric Mann-Whitney test.
(F) Integrin Function-Blocking Antibody prevents axonal regeneration of
Rph3a−/− neurons. Representative
images of Rph3a+/+ and
Rph3a−/− regenerated axons, 7 days
post-axotomy, treated with ß1-Integrin function-blocking antibody and its
respective isotype control. Cortical neurons were stained for
ßIII-tubulin (green) and phalloidin (magenta) to label regenerating axons
and actin-rich growth cones.
(G and H) Graphs represent quantification of axonal regeneration and
actin-rich regenerating growth cones. Data plotted are normalized mean values
± SEM from n = 3 biological replicates with a total of ~200,000
neurons/treatment/experiment. One-way ANOVA with Sidak’s (for F) and
Tukey’s multiple comparison test (for G) statistic applied. **p = 0.0042
(F = 15.21, Df = 11), ****p < 0.0001 (F = 30.3, Df = 11). Scale bar, 200
μm.