title: A model of muscle atrophy based on live microscopy of muscle remodelling in Drosophila metamorphosis.
abstract: Genes controlling muscle size and survival play important roles in muscle wasting diseases. In Drosophila melanogaster metamorphosis, larval abdominal muscles undergo two developmental fates. While a doomed population is eliminated by cell death, another persistent group is remodelled and survives into adulthood. To identify and characterize genes involved in the development of remodelled muscles, we devised a workflow consisting of in vivo imaging, targeted gene perturbation and quantitative image analysis. We show that inhibition of TOR signalling and activation of autophagy promote developmental muscle atrophy in early, while TOR and yorkie activation are required for muscle growth in late pupation. We discovered changes in the localization of myonuclei during remodelling that involve anti-polar migration leading to central clustering followed by polar migration resulting in localization along the midline. We demonstrate that the Cathepsin L orthologue Cp1 is required for myonuclear clustering in mid, while autophagy contributes to central positioning of nuclei in late metamorphosis. In conclusion, studying muscle remodelling in metamorphosis can provide new insights into the cell biology of muscle wasting.
authors.affiliation: Imaging Informatics Division, Bioinformatics Institute (BII), Agency for Science, Technology and Research (ASTAR), 30 Biopolis Street, no. 07-01 Matrix, Singapore 138671, Republic of Singapore; School of Computer Engineering, Nanyang Technological University, N4-2A-05, Nanyang Avenue, Singapore 639798, Republic of Singapore.
authors.forename: Yadav
authors.initials: Y
authors.lastname: Kuleesha
authors.affiliation: Imaging Informatics Division , Bioinformatics Institute (BII), Agency for Science, Technology and Research (ASTAR) , 30 Biopolis Street, no. 07-01 Matrix, Singapore 138671, Republic of Singapore.
authors.forename: Wee Choo
authors.initials: WC
authors.lastname: Puah
authors.affiliation: Imaging Informatics Division , Bioinformatics Institute (BII), Agency for Science, Technology and Research (ASTAR) , 30 Biopolis Street, no. 07-01 Matrix, Singapore 138671, Republic of Singapore.
authors.forename: Martin
authors.initials: M
authors.lastname: Wasser
keywords: Drosophila metamorphosis; autophagy; live imaging; muscle atrophy; muscle remodelling; nuclear migration