Spatial pattern analysis of nuclear migration in remodelled muscles during Drosophila metamorphosis

BMC Bioinformatics

Research Article

Martin Wasser¹  Lin Feng² 

[1] Imaging Informatics Division, Bioinformatics Institute (BII), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore;BioImagingMW, Block 28D Dover Crescent #31-73, 134028, Singapore, Singapore;School of Computer Science and Engineering, Nanyang Technological University, Singapore, Singapore;

关键词: Drosophila metamorphosis;    Myonuclear localization;    Nuclear segmentation;    Nuclear tracking;    Classification;    Feature generation;   

DOI  :  10.1186/s12859-017-1739-0

 received in 2016-11-07, accepted in 2017-06-22,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundMany human muscle wasting diseases are associated with abnormal nuclear localization. During metamorphosis in Drosophila melanogaster, multi-nucleated larval dorsal abdominal muscles either undergo cell death or are remodeled to temporary adult muscles. Muscle remodeling is associated with anti-polar nuclear migration and atrophy during early pupation followed by polar migration and muscle growth during late pupation. Muscle remodeling is a useful model to study genes involved in myonuclear migration. Previously, we showed that loss of Cathepsin-L inhibited anti-polar movements, while knockdown of autophagy-related genes affected nuclear positioning along the medial axis in late metamorphosis.ResultsTo compare the phenotypic effects of gene perturbations on nuclear migration more objectively, we developed new descriptors of myonuclear distribution. To obtain nuclear pattern features, we designed an algorithm to detect and track nuclear regions inside live muscles. Nuclear tracks were used to distinguish between fast moving nuclei associated with fragments of dead muscles (sarcolytes) and slow-moving nuclei inside remodelled muscles. Nuclear spatial pattern features, such as longitudinal (lonNS) and lateral nuclear spread (latNS), allowed us to compare nuclear migration during muscle remodelling in different genetic backgrounds. Anti-polar migration leads to a lonNS decrease. As expected, lack of myonuclear migration caused by the loss of Cp1 was correlated with a significantly lower lonNS decrease. Unexpectedly, the decrease in lonNS was significantly enhanced by Atg9, Atg5 and Atg18 silencing, indicating that the loss of autophagy promotes the migration and clustering of nuclei. Loss of autophagy also caused a scattering of nuclei along the lateral axis, leading to a two-row as opposed to single row distribution in control muscles. Increased latNS resulting from knockdown of Atg9 and Atg18 was correlated with increased muscle diameter, suggesting that the wider muscle fibre promotes lateral displacement of nuclei from the medial axis during polar migration.ConclusionsWe developed new nuclear features to characterize the dynamics of nuclear distribution in time-lapse images of Drosophila metamorphosis. Image quantification improved our understanding of phenotypic abnormalities in nuclear distribution resulting from gene perturbations. Therefore, in vivo imaging and quantitative image analysis of Drosophila metamorphosis promise to provide novel insights into the relationship between muscle wasting and myonuclear positioning.

【 授权许可】

CC BY   
© The Author(s). 2017

【 图 表 】

Fig. 2