Fig. 3
- ID
- ZDB-FIG-230829-14
- Publication
- Weinschutz Mendes et al., 2023 - High-throughput functional analysis of autism genes in zebrafish identifies convergence in dopaminergic and neuroimmune pathways
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Zebrafish mutants of ASD genes display brain size phenotypes (A) Whole-brain volume mapping pipeline (STAR Methods). (B) Eight-region zebrafish brain atlas derived from Thyme et al. (2019) and Randlett et al. (2015).22,42 (C) Hierarchical clustering of regional brain volume measurements comparing mutant and background-matched wild-type fish. Each rectangle in the clustergram represents the signed -log10-transformed p values from linear mixed models (LMM) (red, increased in mutant; blue, decreased in mutant). Regions with significant volume differences by LMM (p < 0.05) are outlined in yellow. p-values for homozygous and heterozygous mutants are shown in Figure S3A. For raw volume quantifications by region for all fish, see Table S3. (D) tERK-immunostained brains of dyrk1aa?77/?77dyrk1ab?8/?8 and wild-type larvae at 6 dpf. Note the decrease in forebrain volume in mutants (arrowheads). Dorsal views. FB, forebrain; OT, optic tectum; CB, cerebellum. Scale bar, 50 ?m. (E) Regional brain volume differences in dyrk1aa?77/?77dyrk1ab?8/?8 (n = 18) and wild-type (n = 18) relative to the standard zebrafish reference brain 42 (dotted line). ????p < 0.0001, ???p < 0.001, ?p < 0.05 (one-way ANOVA). (F) Voxel-wise Z score values representing brain volume differences in dyrk1aa?77/?77dyrk1ab?8/?8 versus background-matched wild-type larvae. Images shown from left to right represent sequential slices: axial views, top row, dorsal to ventral; sagittal views, bottom row, lateral to medial. Scale bar, Z score (red/yellow, increased in mutant; cyan/purple, decreased in mutant). (G) Voxel-wise Z score values representing brain volume differences for the following lines: scn1lab?44/?44, chd8?5/?5, tbr1a?64/?64tbr1b?10/?10, kdm5ba?17/?17kdm5bb?14/?14, and cul3a?7/?7cul3b?20/+. Axial views, top row; sagittal views, bottom row. The horizontal green line in the sagittal view indicates the slice shown in the axial view. FB, forebrain; MHB, midbrain-hindbrain boundary. Scale bar, Z score (red/yellow, increased in mutant; cyan/purple, decreased in mutant). For the number of animals used in imaging experiments, see STAR Methods (average n = 23?26 per genotype in two to four independent clutches). (H) Genotype-level p values for each brain region combined for all homozygous mutants and cul3a?7/?7cul3b?20/+, excluding dyrk1a, using Fisher?s method. Scale represents the -log10-transformed combined p value. The forebrain (telencephalon) shows the most significant difference in volume (p = 8.32 × 10?6, Fisher?s combined probability test). |