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A model of muscle atrophy based on live microscopy of muscle remodelling in Drosophila metamorphosis

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 i...

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Detalles Bibliográficos
Autores principales: Kuleesha, Yadav, Puah, Wee Choo, Wasser, Martin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society Publishing 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4785973/
https://www.ncbi.nlm.nih.gov/pubmed/26998322
http://dx.doi.org/10.1098/rsos.150517
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author Kuleesha, Yadav
Puah, Wee Choo
Wasser, Martin
author_facet Kuleesha, Yadav
Puah, Wee Choo
Wasser, Martin
author_sort Kuleesha, Yadav
collection PubMed
description 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.
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spelling pubmed-47859732016-03-18 A model of muscle atrophy based on live microscopy of muscle remodelling in Drosophila metamorphosis Kuleesha, Yadav Puah, Wee Choo Wasser, Martin R Soc Open Sci Cellular and Molecular biology 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. The Royal Society Publishing 2016-02-10 /pmc/articles/PMC4785973/ /pubmed/26998322 http://dx.doi.org/10.1098/rsos.150517 Text en http://creativecommons.org/licenses/by/4.0/ © 2016 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.
spellingShingle Cellular and Molecular biology
Kuleesha, Yadav
Puah, Wee Choo
Wasser, Martin
A model of muscle atrophy based on live microscopy of muscle remodelling in Drosophila metamorphosis
title A model of muscle atrophy based on live microscopy of muscle remodelling in Drosophila metamorphosis
title_full A model of muscle atrophy based on live microscopy of muscle remodelling in Drosophila metamorphosis
title_fullStr A model of muscle atrophy based on live microscopy of muscle remodelling in Drosophila metamorphosis
title_full_unstemmed A model of muscle atrophy based on live microscopy of muscle remodelling in Drosophila metamorphosis
title_short A model of muscle atrophy based on live microscopy of muscle remodelling in Drosophila metamorphosis
title_sort model of muscle atrophy based on live microscopy of muscle remodelling in drosophila metamorphosis
topic Cellular and Molecular biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4785973/
https://www.ncbi.nlm.nih.gov/pubmed/26998322
http://dx.doi.org/10.1098/rsos.150517
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