Developmentally regulated autophagy is required for eye formation in Drosophila

Viktor Billes, Tibor Kovács, Anna Manzéger, Péter Lőrincz, Sára Szincsák, Ágnes Regős, Péter István Kulcsár, T. Korcsmáros, Tamás Lukácsovich, Gyula Hoffmann, M. Erdélyi, József Mihály, K. Takács-Vellai, M. Sass, T. Vellai

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The compound eye of the fruit fly Drosophila melanogaster 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 (Atg) in the eye primordium severely affects the morphology of the adult eye through triggering ectopic cell death. In Atg 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, Atg8a, is controlled in a complex manner by the anterior Hox paralog Lab (Labial), a master regulator of early development. Atg8a 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 Drosophila 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. Abbreviations: αTub84B, α-Tubulin at 84B; Act5C, Actin5C; 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; exd, extradenticle; ey, eyeless; FLP, flippase recombinase; FRT, FLP recognition target; Gal4, gene encoding the yeast transcription activator protein GAL4; GFP, green fluorescent protein; GMR, Glass multimer reporter; Hox, homeobox; hth, homothorax; lab, labial; 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; w, white.

Original languageEnglish
Pages (from-to)1499-1519
Number of pages21
JournalAutophagy
Volume14
Issue number9
DOIs
Publication statusPublished - Sep 2 2018

Fingerprint

Autophagy
Drosophila
Genes
Lip
RNA Interference
Morphogenesis
Caspase 3
Class III Phosphatidylinositol 3-Kinases
Cell Death
Polymerase Chain Reaction
Acridine Orange
Microtubule-Associated Proteins
DNA Nucleotidylexotransferase
Homeobox Genes
In Situ Nick-End Labeling
Eukaryotic Cells
Sirolimus
Tubulin
Green Fluorescent Proteins
Drosophila melanogaster

Keywords

  • Autophagy
  • cell death
  • differentiation
  • Drosophila
  • eye development
  • genetic compensation
  • HOX
  • labial
  • pattern formation
  • transcriptional control

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Billes, V., Kovács, T., Manzéger, A., Lőrincz, P., Szincsák, S., Regős, Á., ... Vellai, T. (2018). Developmentally regulated autophagy is required for eye formation in Drosophila. Autophagy, 14(9), 1499-1519. https://doi.org/10.1080/15548627.2018.1454569

Developmentally regulated autophagy is required for eye formation in Drosophila. / Billes, Viktor; Kovács, Tibor; Manzéger, Anna; Lőrincz, Péter; Szincsák, Sára; Regős, Ágnes; Kulcsár, Péter István; Korcsmáros, T.; Lukácsovich, Tamás; Hoffmann, Gyula; Erdélyi, M.; Mihály, József; Takács-Vellai, K.; Sass, M.; Vellai, T.

In: Autophagy, Vol. 14, No. 9, 02.09.2018, p. 1499-1519.

Research output: Contribution to journalArticle

Billes, V, Kovács, T, Manzéger, A, Lőrincz, P, Szincsák, S, Regős, Á, Kulcsár, PI, Korcsmáros, T, Lukácsovich, T, Hoffmann, G, Erdélyi, M, Mihály, J, Takács-Vellai, K, Sass, M & Vellai, T 2018, 'Developmentally regulated autophagy is required for eye formation in Drosophila', Autophagy, vol. 14, no. 9, pp. 1499-1519. https://doi.org/10.1080/15548627.2018.1454569
Billes V, Kovács T, Manzéger A, Lőrincz P, Szincsák S, Regős Á et al. Developmentally regulated autophagy is required for eye formation in Drosophila. Autophagy. 2018 Sep 2;14(9):1499-1519. https://doi.org/10.1080/15548627.2018.1454569
Billes, Viktor ; Kovács, Tibor ; Manzéger, Anna ; Lőrincz, Péter ; Szincsák, Sára ; Regős, Ágnes ; Kulcsár, Péter István ; Korcsmáros, T. ; Lukácsovich, Tamás ; Hoffmann, Gyula ; Erdélyi, M. ; Mihály, József ; Takács-Vellai, K. ; Sass, M. ; Vellai, T. / Developmentally regulated autophagy is required for eye formation in Drosophila. In: Autophagy. 2018 ; Vol. 14, No. 9. pp. 1499-1519.
@article{5222173cd96c422b997689b7b26dec7b,
title = "Developmentally regulated autophagy is required for eye formation in Drosophila",
abstract = "The compound eye of the fruit fly Drosophila melanogaster 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 (Atg) in the eye primordium severely affects the morphology of the adult eye through triggering ectopic cell death. In Atg 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, Atg8a, is controlled in a complex manner by the anterior Hox paralog Lab (Labial), a master regulator of early development. Atg8a 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 Drosophila 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. Abbreviations: αTub84B, α-Tubulin at 84B; Act5C, Actin5C; 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; exd, extradenticle; ey, eyeless; FLP, flippase recombinase; FRT, FLP recognition target; Gal4, gene encoding the yeast transcription activator protein GAL4; GFP, green fluorescent protein; GMR, Glass multimer reporter; Hox, homeobox; hth, homothorax; lab, labial; 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; w, white.",
keywords = "Autophagy, cell death, differentiation, Drosophila, eye development, genetic compensation, HOX, labial, pattern formation, transcriptional control",
author = "Viktor Billes and Tibor Kov{\'a}cs and Anna Manz{\'e}ger and P{\'e}ter Lőrincz and S{\'a}ra Szincs{\'a}k and {\'A}gnes Regős and Kulcs{\'a}r, {P{\'e}ter Istv{\'a}n} and T. Korcsm{\'a}ros and Tam{\'a}s Luk{\'a}csovich and Gyula Hoffmann and M. Erd{\'e}lyi and J{\'o}zsef Mih{\'a}ly and K. Tak{\'a}cs-Vellai and M. Sass and T. Vellai",
year = "2018",
month = "9",
day = "2",
doi = "10.1080/15548627.2018.1454569",
language = "English",
volume = "14",
pages = "1499--1519",
journal = "Autophagy",
issn = "1554-8627",
publisher = "Landes Bioscience",
number = "9",

}

TY - JOUR

T1 - Developmentally regulated autophagy is required for eye formation in Drosophila

AU - Billes, Viktor

AU - Kovács, Tibor

AU - Manzéger, Anna

AU - Lőrincz, Péter

AU - Szincsák, Sára

AU - Regős, Ágnes

AU - Kulcsár, Péter István

AU - Korcsmáros, T.

AU - Lukácsovich, Tamás

AU - Hoffmann, Gyula

AU - Erdélyi, M.

AU - Mihály, József

AU - Takács-Vellai, K.

AU - Sass, M.

AU - Vellai, T.

PY - 2018/9/2

Y1 - 2018/9/2

N2 - The compound eye of the fruit fly Drosophila melanogaster 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 (Atg) in the eye primordium severely affects the morphology of the adult eye through triggering ectopic cell death. In Atg 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, Atg8a, is controlled in a complex manner by the anterior Hox paralog Lab (Labial), a master regulator of early development. Atg8a 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 Drosophila 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. Abbreviations: αTub84B, α-Tubulin at 84B; Act5C, Actin5C; 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; exd, extradenticle; ey, eyeless; FLP, flippase recombinase; FRT, FLP recognition target; Gal4, gene encoding the yeast transcription activator protein GAL4; GFP, green fluorescent protein; GMR, Glass multimer reporter; Hox, homeobox; hth, homothorax; lab, labial; 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; w, white.

AB - The compound eye of the fruit fly Drosophila melanogaster 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 (Atg) in the eye primordium severely affects the morphology of the adult eye through triggering ectopic cell death. In Atg 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, Atg8a, is controlled in a complex manner by the anterior Hox paralog Lab (Labial), a master regulator of early development. Atg8a 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 Drosophila 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. Abbreviations: αTub84B, α-Tubulin at 84B; Act5C, Actin5C; 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; exd, extradenticle; ey, eyeless; FLP, flippase recombinase; FRT, FLP recognition target; Gal4, gene encoding the yeast transcription activator protein GAL4; GFP, green fluorescent protein; GMR, Glass multimer reporter; Hox, homeobox; hth, homothorax; lab, labial; 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; w, white.

KW - Autophagy

KW - cell death

KW - differentiation

KW - Drosophila

KW - eye development

KW - genetic compensation

KW - HOX

KW - labial

KW - pattern formation

KW - transcriptional control

UR - http://www.scopus.com/inward/record.url?scp=85052068745&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85052068745&partnerID=8YFLogxK

U2 - 10.1080/15548627.2018.1454569

DO - 10.1080/15548627.2018.1454569

M3 - Article

AN - SCOPUS:85052068745

VL - 14

SP - 1499

EP - 1519

JO - Autophagy

JF - Autophagy

SN - 1554-8627

IS - 9

ER -