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. 2026 Jul 13;16:1814908. doi: 10.3389/fonc.2026.1814908

Figure 2.

Panel A diagram summarizes Drosophila genetic crosses using eyeless-Gal4 with UAS-H2A wild-type, H2A A127V mutant, or control alleles. Panel B shows close-up images of adult fly eyes under control, H2A wild-type, or H2A A127V conditions at 25 and 29 degrees Celsius, revealing morphological differences. Panel C displays several rows of eye images from flies expressing RNAi for different genes with or without H2A variants, a schematic of genotypes tested, and a bar graph quantifying the percentage of flies displaying eye phenotype defects for each genotype.

Screening of AML-related genes in the context of H2A-A127V mutation reveals deleterious or rescuing phenotypic changes. (A) A schematic indicating the flies used in expressing H2A wt and H2A-127V using the eyeless (sensitized) promoter. (B) H2A A 127V induces partial eye phenotypes in the sensitized model (almost all flies had normal eyes, and only 1 out of 100 at 25 °C and 2 out of 100 at 29 °C displayed a more severe phenotype). Light microscopy images of eyes in control, H2A wt, and the H2A-A127V mutants. Three different phenotypes were observed with H2A-A127V varying between small, rough, and tumorous eyes. Upper Panel experiment was performed at 25 °C screening 200 flies and the lower panel experiment was performed at 29 °C screening 100 flies. (C) Light microscopy images of eye phenotypes in H2A wt and H2A-A127V mutants crossed with RNAi lines targeting AML-related genes (n is number of flies screened): ADD1 (1) (Control RNAi n=165, H2A wt n=205, H2A-A127V n=267), ADD1 (2) (Control RNAi n=183, H2A wt n=199, H2A-A127V n=220), Asx (Control RNAi n=182, H2A wt n=201, H2A-A127V n=187), dTet (Control RNAi n=200, H2A wt n=229, H2A-A127V n=252), lozenge (Control RNAi n=237, H2A wt n=204, H2A-A127V n=200), Nlp (Control RNAi n=201, H2A wt n=200, H2A-A127V n=246) and p53 (Control RNAi n=202, H2A wt n=208, H2A-A127V n=207) in a sensitized model. A schematic illustrating the rescue experiments are indicated. Control RNAi was expressed alone in the eye by the sensitized driver that provided the baseline phenotype provoked by the RNAi itself. gfp RNAi is a control for the RNAi system (Control RNAi n=197, H2A wt n=256, H2A-A127V n=214). Scoring eye fold phenotypes (%) in H2A wt (grey bars) and H2A-A127V mutant (black bars) eyes following knockdown of AML-related genes in comparison to Control RNAi (white bars) (*p-value <0.05, **p-value <0.01, ***p-value <0.001 and ****p-value <0.0001; chi-square test). Scale bar, 500µm. Flies were collected from more than 3 biological replicates.