Fully automated leg tracking of Drosophila neurodegeneration models reveals distinct conserved movement signatures
| Autor: | James C. Stewart, Sherry Shiying Aw, Eng-King Tan, Lin Gu, Li Cheng, Joses Ho, Camilo Libedinsky, Adam Claridge-Chang, Boon Hui Wong, Malvika Katarya, Daiqin Li, Lakshmi Narasimhan Govindarajan, Kah Junn Tan, Shuang Wu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Myoclonus
Decision Analysis Movement disorders Physiology Walking Pathology and Laboratory Medicine Machine Learning Gait (human) Animal Cells Image Processing Computer-Assisted Medicine and Health Sciences Drosophila Proteins Biology (General) Gait Musculoskeletal System Neurons Movement Disorders biology Drosophila Melanogaster General Neuroscience Neurodegeneration Methods and Resources Eukaryota Neurodegenerative Diseases Parkinson Disease Machado-Joseph Disease Animal Models Insects Experimental Organism Systems Neurology Spinocerebellar ataxia Legs Engineering and Technology Drosophila Anatomy Cellular Types Drosophila melanogaster medicine.symptom Gait Analysis General Agricultural and Biological Sciences Management Engineering Machado–Joseph disease Drosophila Protein Computer and Information Sciences Arthropoda QH301-705.5 Movement Research and Analysis Methods General Biochemistry Genetics and Molecular Biology Signs and Symptoms Model Organisms Diagnostic Medicine Artificial Intelligence medicine Animals General Immunology and Microbiology Biological Locomotion Decision Trees fungi Organisms Biology and Life Sciences Extremities Cell Biology medicine.disease biology.organism_classification Invertebrates Decision Tree Learning Disease Models Animal Body Limbs Cellular Neuroscience Gait analysis Animal Studies Neuroscience |
| Zdroj: | PLoS Biology, Vol 17, Iss 6, p e3000346 (2019) PLoS Biology |
| ISSN: | 1545-7885 1544-9173 |
| Popis: | Some neurodegenerative diseases, like Parkinsons Disease (PD) and Spinocerebellar ataxia 3 (SCA3), are associated with distinct, altered gait and tremor movements that are reflective of the underlying disease etiology. Drosophila melanogaster models of neurodegeneration have illuminated our understanding of the molecular mechanisms of disease. However, it is unknown whether specific gait and tremor dysfunctions also occur in fly disease mutants. To answer this question, we developed a machine-learning image-analysis program, Feature Learning-based LImb segmentation and Tracking (FLLIT), that automatically tracks leg claw positions of freely moving flies recorded on high-speed video, producing a series of gait measurements. Notably, unlike other machine-learning methods, FLLIT generates its own training sets and does not require user-annotated images for learning. Using FLLIT, we carried out high-throughput and high-resolution analysis of gait and tremor features in Drosophila neurodegeneration mutants for the first time. We found that fly models of PD and SCA3 exhibited markedly different walking gait and tremor signatures, which recapitulated characteristics of the respective human diseases. Selective expression of mutant SCA3 in dopaminergic neurons led to a gait signature that more closely resembled those of PD flies. This suggests that the behavioral phenotype depends on the neurons affected rather than the specific nature of the mutation. Different mutations produced tremors in distinct leg pairs, indicating that different motor circuits were affected. Using this approach, fly models can be used to dissect the neurogenetic mechanisms that underlie movement disorders. This study uses automated leg tracking to characterise gait and tremor features in fruit fly models of Parkinson’s disease and spinocerebellar ataxia 3, finding movement features that resemble characteristics of the respective human diseases. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
| Nepřihlášeným uživatelům se plný text nezobrazuje | K zobrazení výsledku je třeba se přihlásit. |