Fig 2: Delay in regeneration after sciatic nerve injury in Isl1-Dync1h1+/- mice. (A) Representative images of longitudinal cryosections of sciatic nerve stained for Scg10 from WT and Isl1-Dync1h1+/- mice 3 days after injury. Proximal is on the left, distal to the right. Scale bars: 300 µm (main images), 50 µm (higher magnification regions of interest). (B) Quantitative analysis of Scg10 immunoreactivity 1 mm distal to the injury site shows a significant reduction in signal intensity in heterozygous axons compared to WT. Results are mean±s.e.m. (n=8 sections from three biological repeats of the naive, n=20 sections from five biological repeats of injured nerve). **P<0.01, ****P<0.0001, (unpaired two-tailed t-test).

Fig 3: Immunohistochemistry with DYNC1H1 and rhodopsin (Rho) antibodies. (A–D) Representative control (rows A, C) and rodDync1h1-/- retinas (rows B, D) labeled with antibodies directed against DYNC1H1 (rows A, B) and rhodopsin (rows C, D) at P14, P16, P18, P21, and P30. DYNC1H1 is located in the photoreceptor IS and OPL (photoreceptor terminals and bipolar cell dendrites). The rodDync1h1-/- ONL starts to shrink at P16, and only cone nuclei remain at P30. Rhodopsin-containing rod OSs are severely shortened by P21 and absent by P30. Note, almost no rhodopsin accumulates in the ONL. Scale bar: 20 µm. (E) Comparison of the average ONL thickness of control and rodDync1h1-/- central retinas illustrates loss of rod photoreceptors between P16 and P30. Error bars show the standard deviation. *P < 0.05 (Student's t-test). (F) Comparison of the average combined length of rod OS + IS for P10 to P30 control and rodDync1h1-/- retinas shows loss of OS and IS in the absence of DYNC1H1. Error bars show the standard deviation. *P < 0.05 (Student's t-test). For E and F, the numbers of mice for control and rodKO, respectively, were P10, n = 5, 4; P12, n = 8, 3; P14, n = 5, 3; P16, n = 8, 3; P18, n = 3, 3; P21, n = 7, 3; P30, n = 10, 3.

Fig 4: Effect of tamoxifen-induced DYNC1H1 deletion on rhodopsin expression. (A–D) Representative immunohistochemistry from tamDync1h1-/- (first column), uninjected Dync1h1F/F;Prom1-CreERT2 (second column), tamoxifen-injected Dync1h1F/F retinas (third column), and tamoxifen-injected Dync1h1F/+;Prom1-CreERT2 (fourth column) harvested at 1wPTI (A), 2wPTI (B), 3wPTI (C), or 4wPTI (D) and probed with anti-rhodopsin (red). Nuclei were contrasted with DAPI (blue). tamDync1h1-/- retina reveals rod OS shortening and ONL thinning from 2 to 3wPTI. Rod OS shortening and ONL thinning increased in severity by 4wPTI, with minor rhodopsin expression in the ONL. (E–G) Average scotopic ERG traces at 1.4 log cd s·m-2 from control and tamDync1h1-/- at 2wPTI (E), 3wPTI (F), and 4wPTI (G). Scotopic responses decrease between 2 and 4 wPTI in the tamDync1h1-/-.

Fig 5: Influences of maternal high sugar and fat diet on autophagy and neurodevelopment of offspring during the growth stage. (A) Changes on the body weight; (B) Changes on inflammatory factors in serum; (C) the marked proteins expression of KGA/GAD, MAP2, GFAP, Vimentin, IBA1, GAD65, DYNC1H1, Myclin, Tubulin, CHAT, OLIG2 and WFS1 in brain tissues, (D) and the expression LC3A I/LC3A II/ LC3B I/LC3B II protein in brain tissues. The symbol of NA is the 16-month control male samples, NB is the 16-month control female samples; MA is the 16-month HSHF male samples, MB is the 16-month HSHF female samples. Data are presented as the means ± SD of more than 8 independent experiments, and more than 3 independent experiments in Western bolting. *p <0.05 and **p <0.01 vs. the model group by one-way ANOVA, followed by the one-way analysis of variance (ANOVA) at p < 0.05.