Fully automated leg tracking of < i > Drosophila < /i > neurodegeneration models reveals distinct conserved movement signatures

by 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 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 inDrosophila 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 ne...
Source: PLoS Biology: Archived Table of Contents - Category: Biology Authors: Source Type: research