Fig 2: CEP164 disorganization in SFI1-depleted RPE-1 A–DRepresentative widefield images of expanded centrioles in siSFI1-depleted cells stained for tubulin (magenta) and CEP164 (red hot). Each panel shows a different combination of alterations such as normal centriole with normal CEP164 (A), abnormal centriole with normal CEP164 (B), normal centriole with abnormal CEP164 (C), and abnormal centriole with abnormal CEP164 (D). Scale bars: 250 nm.

Fig 3: SFI1 is a centriolar protein co-localizing with Centrin 2 and 3 at the distal tip of centrioles A, BRepresentative confocal images of cycling RPE-1 cells stained for SFI1 (green) and ?-Tubulin (magenta) (A) or SFI1 (green) and Centrin 2/3 (magenta) (B). Scale bar: 5 µm. Dashed-line squares correspond to insets.C, DRepresentative confocal images of expanded centrioles from RPE-1 cells stained for a/ß-tubulin (aßTub, magenta) and SFI1 (green). Right panels show top view images across the centriolar length confirming the distal localization of SFI1 at centrioles. The white arrowhead indicates SFI1 distal dot at centrioles. Scale bars: 200 and 100 nm (right panels). The average position of SFI1 alongside the centriole is shown in (D).E, FRepresentative confocal images of expanded centrioles from RPE-1 cells stained for a/ß-tubulin (aßTub, magenta) and Centrin 2/3 (Cetn2/3, gray). Right panels show top view images across the centriolar length confirming the distal localization of Centrin 2/3 at centrioles. The white arrowhead indicates Centrin 2/3 distal dot at centrioles. Scale bars: 200 and 100 nm (right panels). The average position of Centrin 2/3 alongside the centriole is shown in (F).G, HRepresentative confocal images of expanded centrioles from RPE-1 cells stained for a/ß-tubulin (aßTub, magenta) and Centrin 3 (Cetn3, cyan). Right panels show top view images across the centriolar length confirming the distal localization of Centrin 3 at centrioles. The white arrowhead indicates Centrin 3 distal dot at centrioles. Scale bars: 200 and 100 nm (right panels). The average position of Centrin 3 alongside the centriole is shown in (H).I, JRepresentative confocal images of expanded centrioles from RPE-1 cells stained for a/ß-tubulin (aßTub, magenta), SFI1 (green), and Centrin 2/3 (Cetn3, gray). Right panels show top view images confirming the distal localization of SFI1 and Centrin 2/3 at centrioles. Scale bars: 200 and 100 nm (right panels). The average position of SFI1 and Centrin 2/3 alongside the centriole is shown in (J).K, LPosition of SFI1 and Centrin signals at the distal centriolar region in nm either from separated stainings (K) or co-stainings (L). Data information: Average ± SD, N, statistical analysis: (D) N = 42 centrioles from three independent experiments. (F) N = 26 centrioles from three independent experiments. (H) N = 25 centrioles from three independent experiments. (J) N = 54 centrioles from three independent experiments. (K) SFI1 = 376 ± 18 nm; Centrin 2/3: 355 ± 36 nm; and Centrin 3: 359 ± 37 nm. N = 41, 25, and 24 centrioles for SFI1, Centrin 2/3, and Centrin 3, respectively, from two independent experiments. One-way ANOVA followed by Bonferroni post hoc test (SFI1 vs. Cetn2/3 P = 0.0196, SFI1 vs. Cetn3 P = 0.0702, and Cetn2/3 vs. Cetn3 P = 0.999). (L) SFI1 = 316.3 ± 43.8 nm and Centrin 2/3: 351.8 ± 42.6 nm. N = 53 centrioles from three independent experiments. Unpaired t-test (SFI1 vs. Cetn2/3 **P < 0.0001).

Fig 4: Gallery of defective centrioles in SFI1-depleted RPE-1 cells A, BConfocal images of expanded centrioles from SFI1-depleted RPE-1 stained for a/ß-tubulin (magenta). Top view (top panel) and side view (bottom panels) of broken centriole (A) and abnormal but not broken (B) stained for (a/ß-tubulin, magenta) and SFI1 (green). Scale bar: 200 nm.C, DConfocal images of expanded centrioles from SFI1-depleted RPE-1 stained for a/ß-tubulin (magenta) and CP110 (yellow). Top view (top panel) and side view (bottom panels) of broken centriole (C) and abnormal but not broken (D) stained for (a/ß-tubulin, magenta) and CP110 (yellow). Scale bar: 200 nm.

Fig 5: Expression of Sfi1 mRNA in the PFC and hippocampus from the adult offspring after prenatal poly(I:C) exposure and expression of SFI1 protein and SFI1 mRNA in schizophrenia. (a) Schedule of treatment and behavioral tests. Saline (5 ml/kg/day) or poly(I:C) (5.0 mg/kg/day from E12 to E17) was injected into pregnant mice. Normal food pellets or 0.1% GF food pellets were given to juvenile offspring from D28 to D56. Subsequently, normal food pellets were given to all mice for 14 days (D57-). Brain samples were collected at D70. (b): Sfi1 mRNA in the PFC: There was significant effects (poly(I:C): F1,22 = 25.39, P < 0.001; GF: F1,22 = 20.28, P < 0.001; interaction: F1,22 = 45.97, P < 0.001). (c) Sfi1 mRNA in the hippocampus: There was significant effects (poly(I:C): F1,22 = 9.29, P = 0.006; GF: F1,22 = 6.65, P = 0.017; interaction: F1,22 = 31.01, P < 0.001). The value is expressed as the mean ± S.E.M. (n = 5–7). ***P < 0.001 compared to poly(I:C) + control group. (d) Expression of SFI1 protein in the parietal cortex from patients (n = 15) with schizophrenia was significantly (P = 0.034) higher than that of controls (n = 15). The value is expressed as the mean ± S.D. *P < 0.05 compared to control group. (e) Expression of SFI1 mRNA in the hair-follicle from patients (n = 94) with schizophrenia was significantly (P = 0.002) lower than that of controls (n = 117). The value is expressed as the mean ± S.D. **P < 0.01 compared to control group.