Fig. 7.

Interactions of 16p11.2 homologs with neurodevelopmental genes. a Heatmap of change in phenotype measures (from manual scoring) in two-hit models of flies with knockdown of 16p11.2 homologs with core neurodevelopmental genes (left) or genes within CNV regions (right). Enhancers (orange) and suppressors (blue) for representative interactions of 16p11.2 homologs are shown. b Table summarizing the number of tested interactions of DOC2A^rph, PPP4C^pp4-19C, MAPK3^rl, and KCTD13^CG10465 with 50 neurodevelopmental and genes within other CNV regions. Of the 200 tested interactions measured by manual scoring or Flynotyper, 46 were identified as suppressors or enhancers of one-hit phenotype, and were validated in multiple RNAi or deficiency lines when available. c Representative brightfield adult eye images (scale bar = 50 µm) and box plots of Flynotyper scores for simultaneous knockdowns of KCTD13^CG10465, MAPK3^rl, PPP4C^pp4-19C, and DOC2A^rph with neurodevelopmental genes (n = 5–13, *p < 0.05, Mann–Whitney test). d Representative confocal images of pupal eye (scale bar = 5 µm) and larval eye discs (scale bar = 30 µm) of the MAPK3^rl/PTEN^dpten two-hit knockdown flies, stained with anti-Dlg and anti-pH3 respectively. e Box plot of photoreceptor cell count in the pupal eye of MAPK3^rl and PTEN^dpten one-hit and two-hit flies (n = 58-65, *p = 3.62 × 10^–15 compared to one-hit knockdown of MAPK3^rl, Mann–Whitney test). f Box plot of pH3-positive cells in the larval eye between MAPK3^rl and PTEN^dpten one-hit and two-hit flies (n = 9, *p = 0.00174 compared to one-hit knockdown of MAPK3^rl, Mann-Whitney test). All boxplots indicate median (center line), 25th and 75th percentiles (bounds of box), and minimum and maximum (whiskers)