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Fig. 6

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ZDB-IMAGE-211126-12
Source
Figures for Jamadagni et al., 2021
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Figure Caption

Fig. 6 A. Movement scores of chd-7(gk290) mutants (red) compared with N2 wildtype (WT; black). Two-tailed t-test was performed for statistical analyses, and movement score was considered different to WT (N = 3, n = 30; ****P < 0.0001, Student’s t-test). B. Lifespan analyses of chd-7(gk290) mutants (n = 339; red) compared with WT (n = 444; black). Log-rank test was performed for statistical analyses. ***P < 0.001. C. WT and chd-7(gk290) animals with defects in the GABAergic (black) and cholinergic nervous system (grey) at the L4 stage (N = 4, n = 100; ****P < 0.0001; Student’s t-test). D–F. Example pictures of the GABAergic nervous system cell bodies, commissures, axonal gaps and axonal breaks larger than 50 µm per worm in chd-7(gk290) mutants expressing unc-47p::mCherry. G–I. GABAergic neurodevelopmental defects of WT (black) and chd-7(gk290) mutants (grey) at the L4 stage classified in axonal gaps per worm (G), number of GABAergic cell bodies (H) and number of commissures (I). N = 4, n = 100; ****P < 0.0001, Student’s t-test. J. Chemical libraries (3,850 compounds) were first screen in chd-7(gk290) C. elegans mutants and positive hits were tested on chd7 zebrafish mutants. K. 49 compounds that improved motility phenotypes in chd-7(gk290) mutants were identified. These compounds were clustered in 6 main functional categories. L. Movement scores of chd-7(gk290) mutants treated with ephedrine (blue) compared with the solvent DMSO (black). N = 3, n > 100; ****P < 0.0001, Student’s t-test. M. Defects of the GABAergic nervous system at the L4 stage in chd-7(gk290) mutants treated with ephedrine (grey) compared with DMSO (black) (N = 3, n > 100). ****P < 0.0001, Student’s t-test. N. Average activity per second is wild-type and mutants treated with ephedrine compared with non-treated mutant (wild-type treated with ephedrine is referred to as Control). Ephedrine suppresses hyperactivity in chd7 mutant fish. n = 24; ****P < 0.0001, one-way ANOVA. O. Representative images of GABAergic neurons and total number of GABAergic neurons (GFP+ cells) in the optic tectum (OT) and cerebellum (CB) regions of wild-type, chd7 mutant and ephedrine-treated fish (n = 9; ****P < 0.0001; One-way ANOVA). Treatment with ephedrine ameliorated the number of GABAergic neurons. P, Q. pERK is reduced in mutants following treatment with ephedrine as shown by Western blot quantification (N = 4). ****P < 0.0001, one-way ANOVA. R. qPCR analysis of paqr3b expression in chd7+/+, chd7−/− and chd7−/− treated with ephedrine (N = 4; ****P < 0.0001; ns, not significant, one-way ANOVA).

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