Illuminating ALS Motor Neurons With Optogenetics in Zebrafish
Amyotrophic lateral sclerosis (ALS) is a fatal neurological disorder characterized by progressive degeneration of motor neurons in the brain and spinal cord. Spinal motor neurons align along the spinal cord length within the vertebral column, and extend long axons to connect with skeletal muscles co...
প্রধান লেখক: | , , |
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বিন্যাস: | প্রবন্ধ |
ভাষা: | English |
প্রকাশিত: |
Frontiers Media S.A.
2021-03-01
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মালা: | Frontiers in Cell and Developmental Biology |
বিষয়গুলি: | |
অনলাইন ব্যবহার করুন: | https://www.frontiersin.org/articles/10.3389/fcell.2021.640414/full |
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author | Kazuhide Asakawa Hiroshi Handa Koichi Kawakami Koichi Kawakami |
author_facet | Kazuhide Asakawa Hiroshi Handa Koichi Kawakami Koichi Kawakami |
author_sort | Kazuhide Asakawa |
collection | DOAJ |
description | Amyotrophic lateral sclerosis (ALS) is a fatal neurological disorder characterized by progressive degeneration of motor neurons in the brain and spinal cord. Spinal motor neurons align along the spinal cord length within the vertebral column, and extend long axons to connect with skeletal muscles covering the body surface. Due to this anatomy, spinal motor neurons are among the most difficult cells to observe in vivo. Larval zebrafish have transparent bodies that allow non-invasive visualization of whole cells of single spinal motor neurons, from somas to the neuromuscular synapses. This unique feature, combined with its amenability to genome editing, pharmacology, and optogenetics, enables functional analyses of ALS-associated proteins in the spinal motor neurons in vivo with subcellular resolution. Here, we review the zebrafish skeletal neuromuscular system and the optical methods used to study it. We then introduce a recently developed optogenetic zebrafish ALS model that uses light illumination to control oligomerization, phase transition and aggregation of the ALS-associated DNA/RNA-binding protein called TDP-43. Finally, we will discuss how this disease-in-a-fish ALS model can help solve key questions about ALS pathogenesis and lead to new ALS therapeutics. |
first_indexed | 2024-12-19T13:40:30Z |
format | Article |
id | doaj.art-9e9533f958d7407584eb443c5b8923f4 |
institution | Directory Open Access Journal |
issn | 2296-634X |
language | English |
last_indexed | 2024-12-19T13:40:30Z |
publishDate | 2021-03-01 |
publisher | Frontiers Media S.A. |
record_format | Article |
series | Frontiers in Cell and Developmental Biology |
spelling | doaj.art-9e9533f958d7407584eb443c5b8923f42022-12-21T20:19:01ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-03-01910.3389/fcell.2021.640414640414Illuminating ALS Motor Neurons With Optogenetics in ZebrafishKazuhide Asakawa0Hiroshi Handa1Koichi Kawakami2Koichi Kawakami3Department of Chemical Biology, Tokyo Medical University, Tokyo, JapanDepartment of Chemical Biology, Tokyo Medical University, Tokyo, JapanDivision of Molecular and Developmental Biology, National Institute of Genetics, Mishima, JapanDepartment of Genetics, Graduate University for Advanced Studies (SOKENDAI), Mishima, JapanAmyotrophic lateral sclerosis (ALS) is a fatal neurological disorder characterized by progressive degeneration of motor neurons in the brain and spinal cord. Spinal motor neurons align along the spinal cord length within the vertebral column, and extend long axons to connect with skeletal muscles covering the body surface. Due to this anatomy, spinal motor neurons are among the most difficult cells to observe in vivo. Larval zebrafish have transparent bodies that allow non-invasive visualization of whole cells of single spinal motor neurons, from somas to the neuromuscular synapses. This unique feature, combined with its amenability to genome editing, pharmacology, and optogenetics, enables functional analyses of ALS-associated proteins in the spinal motor neurons in vivo with subcellular resolution. Here, we review the zebrafish skeletal neuromuscular system and the optical methods used to study it. We then introduce a recently developed optogenetic zebrafish ALS model that uses light illumination to control oligomerization, phase transition and aggregation of the ALS-associated DNA/RNA-binding protein called TDP-43. Finally, we will discuss how this disease-in-a-fish ALS model can help solve key questions about ALS pathogenesis and lead to new ALS therapeutics.https://www.frontiersin.org/articles/10.3389/fcell.2021.640414/fullRNA metabolismphase transitionneurodegenarative diseaseoptogeneticsprotein aggregation |
spellingShingle | Kazuhide Asakawa Hiroshi Handa Koichi Kawakami Koichi Kawakami Illuminating ALS Motor Neurons With Optogenetics in Zebrafish Frontiers in Cell and Developmental Biology RNA metabolism phase transition neurodegenarative disease optogenetics protein aggregation |
title | Illuminating ALS Motor Neurons With Optogenetics in Zebrafish |
title_full | Illuminating ALS Motor Neurons With Optogenetics in Zebrafish |
title_fullStr | Illuminating ALS Motor Neurons With Optogenetics in Zebrafish |
title_full_unstemmed | Illuminating ALS Motor Neurons With Optogenetics in Zebrafish |
title_short | Illuminating ALS Motor Neurons With Optogenetics in Zebrafish |
title_sort | illuminating als motor neurons with optogenetics in zebrafish |
topic | RNA metabolism phase transition neurodegenarative disease optogenetics protein aggregation |
url | https://www.frontiersin.org/articles/10.3389/fcell.2021.640414/full |
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