Extended Data Fig. 7: Characterization of TDP-43 behavior in intact and injured brains.
a, Representative images of HuC/D (magenta) and TDP-43 (cyan) immunoreactivity in intact Wt (grna+/+;grnb+/+) telencephalon. Scale bars, 20 µm. b, Representative images of DAPI (magenta) and TDP-43 (cyan) immunoreactivity in injured Wt (grna+/+;grnb+/+) telencephalon at 3 dpi. Scale bars, 20 µm. Red arrowheads indicate examples of extranuclear TDP-43+ condensates; white arrowheads indicate examples of nuclear TDP-43+ signal. c, Representative images of 4C4 (magenta) and TDP-43 (cyan) immunoreactivity with orthogonal projections at injury sites in Wt (grna+/+;grnb+/+) and Grn-deficient (grna−/−;grnb−/−) brains at 3 dpi, displaying colocalization of TDP-43+ condensates with 4C4+ microglia. Scale bars, 20 µm. d, Representative images of phosphoTDP-43 (cyan), Plin3 (green) and Lamp1 (magenta) immunoreactivity in injured (3 dpi) Wt (grna+/+;grnb+/+) and Grn-deficient (grna−/−;grnb−/−) telencephali. Scale bars, 20 µm. e, Experimental paradigm of intraparenchymal recombinant PGRN injection in Grn-deficient brain. f, Representative images of 4C4 (magenta) and TDP-43 (cyan) immunoreactivity at injury sites in vehicle- and PGRN-injected Grn-deficient (grna−/−;grnb−/−) brains. Scale bars, 20 µm. g,h, Dot plots depicting the numbers of TDP-43+ condensates (g) and TDP-43+ condensates in 4C4+ microglia (h) at injury sites in Wt (grna+/+;grnb+/+), Grn-deficient (grna−/−;grnb−/−) and PGRN-injected Grn-deficient (grna−/−;grnb−/−) brains at 7 dpi. Data are shown as mean ± SEM. n = 4 per group. Each point represents one animal. Significance was calculated with ordinary one-way ANOVA, with post-hoc Tukey’s test for multiple comparisons.
