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Automated leg tracking reveals distinct conserved gait and tremor signatures in Drosophila models of Parkinson’s Disease and Spinocerebellar ataxia 3

Shuang Wu, Kah Junn Tan, Lakshmi Narasimhan Govindarajan, James Charles Stewart, Lin Gu, Joses Wei Hao Ho, Malvika Katarya, Boon Hui Wong, Eng-King Tan, Daiqin Li, Adam Claridge-Chang, Camilo Libedinsky, Li Cheng, View ORCID ProfileSherry Shiying Aw
doi: https://doi.org/10.1101/425405
Shuang Wu
1Bioinformatics Institute, Agency for Science, Technology and Research, 30 Biopolis Street, Singapore 138671
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Kah Junn Tan
2Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, 61 Biopolis Drive, Singapore 138673
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  • For correspondence: chengli@bii.a-star.edu.sg syaw@imcb.a-star.edu.sg
Lakshmi Narasimhan Govindarajan
1Bioinformatics Institute, Agency for Science, Technology and Research, 30 Biopolis Street, Singapore 138671
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  • For correspondence: chengli@bii.a-star.edu.sg syaw@imcb.a-star.edu.sg
James Charles Stewart
2Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, 61 Biopolis Drive, Singapore 138673
3Duke-NUS Graduate Medical School, Neuroscience and Behavioural Disorders, 8 College Road, Singapore 169857
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Lin Gu
1Bioinformatics Institute, Agency for Science, Technology and Research, 30 Biopolis Street, Singapore 138671
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Joses Wei Hao Ho
2Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, 61 Biopolis Drive, Singapore 138673
3Duke-NUS Graduate Medical School, Neuroscience and Behavioural Disorders, 8 College Road, Singapore 169857
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Malvika Katarya
2Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, 61 Biopolis Drive, Singapore 138673
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Boon Hui Wong
4National University of Singapore, Department of Biological Sciences, 14 Science Drive 4, Singapore 117543
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Eng-King Tan
5National Neuroscience Institute, Singapore General Hospital, 20 College Road, The Academia, Singapore 169856
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Daiqin Li
4National University of Singapore, Department of Biological Sciences, 14 Science Drive 4, Singapore 117543
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Adam Claridge-Chang
2Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, 61 Biopolis Drive, Singapore 138673
3Duke-NUS Graduate Medical School, Neuroscience and Behavioural Disorders, 8 College Road, Singapore 169857
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Camilo Libedinsky
2Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, 61 Biopolis Drive, Singapore 138673
6Singapore Institute for Neurotechnology (SiNAPSE), 28 Medical Drive, Singapore 117456
7National University of Singapore, Department of Psychology, Block AS4, 9 Arts Link, Singapore 117570
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Li Cheng
1Bioinformatics Institute, Agency for Science, Technology and Research, 30 Biopolis Street, Singapore 138671
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  • For correspondence: chengli@bii.a-star.edu.sg syaw@imcb.a-star.edu.sg
Sherry Shiying Aw
2Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, 61 Biopolis Drive, Singapore 138673
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  • ORCID record for Sherry Shiying Aw
  • For correspondence: chengli@bii.a-star.edu.sg syaw@imcb.a-star.edu.sg
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Summary

Genetic models in Drosophila have made invaluable contributions to our understanding of the molecular mechanisms underlying neurodegeneration. In human patients, some neurodegenerative diseases lead to characteristic movement dysfunctions, such as abnormal gait and tremors. However, it is currently unknown whether similar movement defects occur in the respective fly models, which could be used to model and better understand the pathophysiology of movement disorders. To address this question, we developed a machine-learning image-analysis programme — Feature Learning-based LImb segmentation and Tracking (FLLIT) — that automatically tracks leg claw positions of freely moving flies recorded on high-speed video, generating a series of body and leg movement parameters. Of note, FLLIT requires no user input for learning. We used FLLIT to characterise fly models of Parkinson’s Disease (PD) and Spinocerebellar ataxia 3 (SCA3). Between these models, walking gait and tremor characteristics differed markedly, and recapitulated signatures of the respective human diseases. Selective expression of mutant SCA3 in dopaminergic neurons led to phenotypes resembling that of PD flies, suggesting that the behavioural phenotype may depend on the circuits affected, rather than the specific nature of the mutation. Different mutations produced tremors in distinct leg pairs, indicating that different motor circuits are affected. Almost 190,000 video frames were tracked in this study, allowing, for the first time, high-throughput analysis of gait and tremor features in Drosophila mutants. As an efficient assay of mutant gait and tremor features in an important model system, FLLIT will enable the analysis of the neurogenetic mechanisms that underlie movement disorders.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted September 25, 2018.
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Automated leg tracking reveals distinct conserved gait and tremor signatures in Drosophila models of Parkinson’s Disease and Spinocerebellar ataxia 3
Shuang Wu, Kah Junn Tan, Lakshmi Narasimhan Govindarajan, James Charles Stewart, Lin Gu, Joses Wei Hao Ho, Malvika Katarya, Boon Hui Wong, Eng-King Tan, Daiqin Li, Adam Claridge-Chang, Camilo Libedinsky, Li Cheng, Sherry Shiying Aw
bioRxiv 425405; doi: https://doi.org/10.1101/425405
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Automated leg tracking reveals distinct conserved gait and tremor signatures in Drosophila models of Parkinson’s Disease and Spinocerebellar ataxia 3
Shuang Wu, Kah Junn Tan, Lakshmi Narasimhan Govindarajan, James Charles Stewart, Lin Gu, Joses Wei Hao Ho, Malvika Katarya, Boon Hui Wong, Eng-King Tan, Daiqin Li, Adam Claridge-Chang, Camilo Libedinsky, Li Cheng, Sherry Shiying Aw
bioRxiv 425405; doi: https://doi.org/10.1101/425405

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