Fig. 1

NPC1 and NPC2 deficiencies lead to ameboid microglia under phagocytic stress.a Schematic of the CRISPANT workflow created in BioRender. Zareba, J. (2022) BioRender.com/v30d049. b?f Representative images of OT zebrafish microglia (Tg(mpeg1.1:EGFP-CAAX)). Scale bar 50 µm. Boxes with magnifications of single microglia (TgBAC(csf1ra:GAL4-VP16), Tg(UAS-E1B:NTR-mCherry)). Scale bar 10 µm. Wild-type (b), NPC1 CRISPANT (c), NPC2 CRISPANT (d), NPC1 / NPC2 CRISPANT (e), wild-type treated with U18666a (f). g Circularity of OT microglia in wild-type (N = 10, n = 207), NPC1 CRISPANT (N = 14, n = 230), NPC2 CRISPANT (N = 10, n = 193), NPC1 / NPC2 CRISPANT (N = 6, n = 115) and wild-type zebrafish treated with U18666a (N = 10, n = 223). h Representative images of OT zebrafish microglia (TgBAC(csf1ra:GAL4-VP16), Tg(UAS-E1B:NTR-mCherry)). Branches indicated by orange arrowheads. Scale bar 10 µm. i Number of branches per OT microglia from wild-type (N = 3, n = 54), NPC1 CRISPANT (N = 6, n = 85) and wild-type treated with U18666a (N = 4, n = 95) zebrafish. j Schematic of the zebrafish brain regions. k Representative images of HB zebrafish microglia (TgBAC(csf1ra:GAL4-VP16), Tg(UAS-E1B:NTR-mCherry)). Scale bar 10 µm. l Circularity of HB zebrafish microglia from wild-type (N = 8, n = 16), wild-type treated with CPT (N = 15, n = 28), NPC1 CRISPANT (N = 7, n = 16) and NPC1 CRISPANT treated with CPT (N = 12, n = 28). N refers to the number of zebrafish embryos and n to the number of microglia examined. Boxplots represent the median value and interquartile range; the ends of the whiskers correspond to the minimum and maximum values. Statistical tests: Mann-Whitney-Wilcoxon test two-sided with Bonferroni correction. ns without any additional p value on the graph stands for p = 1. OT stands for optic tectum and HB stands for hindbrain. Source data are provided as a Source Data file.