Fig. 5

Comparison of letm1+/+ and letm1−/− compensators versus non-compensators. (A, B, C, D) Representative images of zebrafish larvae at 4 day post fertilization, wild type (WT) (A), letm1−/− compensators (C) (B), and letm1−/− non-compensators (NC) (C, D), sampled for RNA sequencing. Scale bar = 1 mm. (E, F, G) Gene set enrichment analysis grouped in clusters according to gene ontology terms. (E, F, G) Up-regulated clusters (orange) and down-regulated clusters (blue) are shown for each pairwise comparison C versus NC (E), C versus WT (F), and NC versus WT (G). The threshold was set to P (adjusted) value = 0.05 and log₂ fold change = ±1. (H) Schematic showing the kynurenine pathway and Preiss–Handler and salvage pathways for NAD production, where certain enzymes are down-regulated in NC and C. NC: letm1−/− non-compensators and C: letm1−/− compensators. Dashed lines indicate intermediate metabolic steps. (I) Heat map of expression of enzymes involved in the different pathways of NAD production in pairwise comparisons C versus NC, C versus WT, and NC versus WT. Stars indicate the significance of the adjusted P-value obtained with the Benjamini–Hochberg method (*P-value < 0.05; **P-value < 0.01; ***P-value < 0.001).