Direct evaluation of neuroaxonal degeneration with the causative genes of neurodegenerative diseases in Drosophila using the automated axon quantification system, MeDUsA

Author:

Nitta Yohei1,Kawai Hiroki2,Maki Ryuto3,Osaka Jiro3,Hakeda-Suzuki Satoko3,Nagai Yoshitaka45,Doubková Karolína67,Uehara Tomoko8,Watanabe Kenji9,Kosaki Kenjiro10,Suzuki Takashi3,Tavosanis Gaia6711,Sugie Atsushi1ORCID

Affiliation:

1. Brain Research Institute, Niigata University , Niigata 951-8585 , Japan

2. LPIXEL Inc. , Tokyo 100-0004 , Japan

3. School of Life Science and Technology, Tokyo Institute of Technology , Yokohama 226-8501 , Japan

4. Osaka University Graduate School of Medicine Department of Neurotherapeutics, , Suita 565-0871 , Japan

5. Kindai University Faculty of Medicine Department of Neurology, , Osaka-Sayama 589-8511 , Japan

6. German Center for Neurodegenerative Diseases (DZNE) , Bonn 53127 , Germany

7. RWTH Aachen Institut für Entwicklungsbiologie , Worringerweg Aachen 352074 , Germany

8. Aichi Developmental Disability Center Hospital Division of Clinical Genetics, , Kasugai 480-0392 , Japan

9. Kagoshima City Hospital Department of Pediatrics, , Kagoshima 890-8760 , Japan

10. Center for Medical Genetics, Keio University School of Medicine , Tokyo 160-8582 , Japan

11. LIMES Institute, University of Bonn , Bonn 53127 , Germany

Abstract

Abstract Drosophila is an excellent model organism for studying human neurodegenerative diseases (NDs). However, there is still almost no experimental system that could directly observe the degeneration of neurons and automatically quantify axonal degeneration. In this study, we created MeDUsA (a ‘method for the quantification of degeneration using fly axons’), a standalone executable computer program based on Python that combines a pre-trained deep-learning masking tool with an axon terminal counting tool. This software automatically quantifies the number of retinal R7 axons in Drosophila from a confocal z-stack image series. Using this software, we were able to directly demonstrate that axons were degenerated by the representative causative genes of NDs for the first time in Drosophila. The fly retinal axon is an excellent experimental system that is capable of mimicking the pathology of axonal degeneration in human NDs. MeDUsA rapidly and accurately quantifies axons in Drosophila photoreceptor neurons. It enables large-scale research into axonal degeneration, including screening to identify genes or drugs that mediate axonal toxicity caused by ND proteins and diagnose the pathological significance of novel variants of human genes in axons.

Funder

Japan Agency for Medical Research and Development

Ministry of Education

Publisher

Oxford University Press (OUP)

Subject

Genetics (clinical),Genetics,Molecular Biology,General Medicine

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