Fig. 7: A tug-of-war between WNT and FGF regulates chromosome segregation fidelity in mouse neural progenitors. | Nature Communications

Fig. 7: A tug-of-war between WNT and FGF regulates chromosome segregation fidelity in mouse neural progenitors.

From: Developmental signals control chromosome segregation fidelity during pluripotency and neurogenesis by modulating replicative stress

Fig. 7

a–c Immunofluorescence analyses of the activated WNT (LRP6) and FGF (FGFR1) receptors in the ventricular zone of E12.5-16.5 embryonic mouse brains. Quantification of phospho-LRP6 (S1490) (b) and phospho-FGFR1 (Y154) (c) in NPCs from the ventricular zone of mouse embryos is shown for three developmental stages of cortical neurogenesis. Data are mean ± s.d. of the relative fluorescence intensity normalised to Nestin in apical neural progenitors of n > 5 brain cryosections from n = 3 embryos of each condition. P-values from one-way ANOVA analyses with multiple comparisons with Dunnet corrections are indicated as ***P < 0.001, or n.s. (P > 0.05, not significant). d Chromosome segregation analyses in ex vivo cultured NPCs from E12.5 and E14.5 mouse embryos, treated as indicated for 16 h. Data are mean ± s.d. of chromosome missegregation rates from n = 3 biological replicates with >50 anaphases per condition in each replicate. In each experiment, mNPCs dissociated from n > 3 mouse embryo brains were pooled together for seeding. P-values from two-way ANOVA analyses with multiple comparisons and Tukey corrections are indicated as **P < 0.01, ***P < 0.001, or n.s. (P > 0.05, not significant). e, f Accumulation of γ-H2AX foci in S-phase of E14.5-derived NPCs treated for 3 h as indicated. Data are the MFI in n > 200 EdU+ nuclei from a representative experiment out of three biological replicates. P-values from one-way ANOVA analyses with multiple comparisons with Dunnet corrections are indicated as ***P < 0.001. g Chromosome segregation analyses in ex vivo cultured NPCs from E14.5 mouse embryos, treated as indicated for 16 h. Data are chromosome missegregation rates plotted as mean ± s.d. from n = 3 biological replicates with 50–100 anaphases analysed per condition and per replicate. P-values from one-way ANOVA analyses with multiple comparisons with Dunnet corrections are indicated as ***P < 0.001. h Schematics of in utero ventricular injections of PBS (control) or recombinant DKK1 in E13.5 mouse embryos, later sacrificed at stage E14.5. i, j Chromosome segregation analyses in the ventricular zone of PBS (Control) or DKK1 injected mouse E14.5 embryos. Data are mean ± s.d. of three injected embryos per condition (>10 cryosections per embryo). P-values from a two-tailed t-test are indicated as *P = 0.029. k A tug-of-war between WNT and FGF controls chromosome segregation fidelity in NPCs, and might underlie the high levels of chromosome missegregation occurring during neurogenesis. Scale bars = 10 μm. Source data for all experiments are provided as a Source data file. h, k Created with BioRender.com released under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International license139.

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