Fig. 6: Genetic screens reveal the function of astrocyte-derived GLaz in dendrite development and lipid homeostasis.

a Astrocyte processes (labeled by Alrm-Gal4 driving CD8::GFP, green) and LNv dendrites (labeled by Pdf-lexA driving LexAop-tdTomato, red) show close interactions with the LON (observed in at least 10 brains). b A schematic representation of analyses performed to identify potential astrocyte-derived ligands for LpR1-short. Candidate lipoproteins were found by combined bioinformatic analyses and genetic screens of fly homologs of human lipid transfer proteins enriched in astrocytes. Genetic screens were performed using astrocyte-specific RNAi knock-down of candidate genes and subsequent quantification of LNv dendrite volume. c Quantifications of LNv dendrite volume. Transgenic RNAi knock-down of lipid transport proteins GLaz, CG12926, and CG30392 in astrocytes leads to significant LNv dendrite volume reduction. Data are presented as mean values +/− SEM. Statistical significance was assessed by a two-tailed Student’s t-test comparing with the control sample. GLaz (1): p = 0.0297, t = 2.333, df = 21; GLaz (2): p = 0.0097, t = 2.846, df = 21; CG12926: p = 0.0075, t = 2.956, df = 21; CG30392: p = 0.0044, t = 3.194, df = 21; CG9205: p = 0.1874, t = 1.363, df = 21; Npc2b: p = 0.2483, t = 1.183, df = 24; CG32407: p = 0.0550, t = 2.038, df = 20; apolpp: p = 0.1263, t = 1.592, df = 21; Apoltp: p = 0.0831, t = 1.820, df = 21; CG11151: p = 0.1164, t = 1.638, df = 21; NLaz: p = 0.1178, t = 1.631, df = 21; pinta: p = 0.0721, t = 1.899, df = 20; Spcx: p = 0.1057, t = 1.684, df = 23; CG5590: p = 0.6180, t = 0.5062, df = 21. n = 13, 10, 10, 10, 10, 10, 13, 9, 10, 10, 10, 10, 9, 12, and 10 for control, GLaz (1), GLaz (2), CG12926, CG30392, CG9205, Npc2b, CG32407, apolpp, Apoltp, CG11151, NLaz, pinta, Spcx, and CG5590. n represents individual larval brain samples. *p < 0.05, **p < 0.01. d Representative projected confocal images showing the reduced LNv dendrite volume (red) by knocking down GLaz in astrocytes (green) (repeated in at least 10 brains). e–f Astrocyte-derived GLaz regulates lipid droplet density in LON. Representative projected confocal images (e) and quantifications (f) showing that lipid droplet density in LON is reduced when GLaz expression is knocked down in astrocytes. Data in f are presented as mean values +/− SEM. Statistical significance was assessed by a two-tailed Student’s t-test. p < 0.0001, t = 6.178, df = 21. n = 12 and 11 for control and GLaz IR. n represents individual larval brain samples. ***p < 0.001.