Developmentally regulated autophagy is required for eye formation in <i>Drosophila</i>
Creators: name: Billes, Viktor
name: Kovács, Tibor
name: Manzéger, Anna
name: Lőrincz, Péter
name: Szincsák, Sára
name: Regős, Ágnes
name: Kulcsár, Péter István
name: Korcsmáros, Tamás
name: Lukácsovich, Tamás
name: Hoffmann, Gyula
name: Erdélyi, Miklós
name: Mihály, József
name: Takács-Vellai, Krisztina
name: Sass, Miklós
name: Vellai, Tibor
Publisher: name: Taylor & Francis
Year: 2019
Subjects: subject: Biophysics
subject: Biochemistry
subject: Cell Biology
subject: Genetics
subject: FOS: Biological sciences
subject: Molecular Biology
subject: Developmental Biology
subject: Inorganic Chemistry
subject: FOS: Chemical sciences

description: The compound eye of the fruit fly <i>Drosophila melanogaster</i> is one of the most intensively studied and best understood model organs in the field of developmental genetics. Herein we demonstrate that autophagy, an evolutionarily conserved selfdegradation process of eukaryotic cells, is essential for eye development in this organism. Autophagic structures accumulate in a specific pattern in the developing eye disc, predominantly in the morphogenetic furrow (MF) and differentiation zone. Silencing of several autophagy genes (<i>Atg</i>) in the eye primordium severely affects the morphology of the adult eye through triggering ectopic cell death. In <i>Atg</i> mutant genetic backgrounds however genetic compensatory mechanisms largely rescue autophagic activity in, and thereby normal morphogenesis of, this organ. We also show that in the eye disc the expression of a key autophagy gene, <i>Atg8a</i>, is controlled in a complex manner by the anterior Hox paralog Lab (Labial), a master regulator of early development. <i>Atg8a</i> transcription is repressed in front of, while activated along, the MF by Lab. The amount of autophagic structures then remains elevated behind the moving MF. These results indicate that eye development in <i>Drosophila</i> depends on the cell death-suppressing and differentiating effects of the autophagic process. This novel, developmentally regulated function of autophagy in the morphogenesis of the compound eye may shed light on a more fundamental role for cellular self-digestion in differentiation and organ formation than previously thought. <b>Abbreviations</b>: αTub84B, α-Tubulin at 84B; <i>Act5C, Actin5C</i>; AO, acridine orange; Atg, autophagy-related; Ato, Atonal; CASP3, caspase 3; Dcr-2; Dicer-2; Dfd, Deformed; DZ, differentiation zone; eGFP, enhanced green fluorescent protein; EM, electron microscopy; <i>exd, extradenticle; ey, eyeless</i>; FLP, flippase recombinase; FRT, FLP recognition target; <i>Gal4</i>, gene encoding the yeast transcription activator protein GAL4; GFP, green fluorescent protein; GMR, Glass multimer reporter; Hox, homeobox; <i>hth, homothorax; lab, labial</i>; L3F, L3 feeding larval stage; L3W, L3 wandering larval stage; lf, loss-of-function; MAP1LC3, microtubule-associated protein 1 light chain 3; MF, morphogenetic furrow; PE, phosphatidylethanolamine; PBS, phosphate-buffered saline; PI3K/PtdIns3K, class III phosphatidylinositol 3-kinase; PZ, proliferation zone; Ref(2)P, refractory to sigma P, RFP, red fluorescent protein; RNAi, RNA interference; RpL32, Ribosomal protein L32; RT-PCR, reverse transcription-coupled polymerase chain reaction; S.D., standard deviation; SQSTM1, Sequestosome-1, Tor, Target of rapamycin; TUNEL, terminal deoxynucleotidyl transferase mediated dUTP nick end labeling assay; UAS, upstream activation sequence; qPCR, quantitative real-time polymerase chain reaction; <i>w, white</i>