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Restoration of the defect in radial glial fiber migration and cortical plate organization in a brain organoid model of Fukuyama muscular dystrophy
Fukuyama congenital muscular dystrophy (FCMD) is a severe, intractable genetic disease that affects the skeletal muscle, eyes, and brain and is attributed to a defect in alpha dystroglycan (αDG) O-mannosyl glycosylation. We previously established disease models of FCMD; however, they did not fully r...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487058/ https://www.ncbi.nlm.nih.gov/pubmed/34632335 http://dx.doi.org/10.1016/j.isci.2021.103140 |
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author | Taniguchi-Ikeda, Mariko Koyanagi-Aoi, Michiyo Maruyama, Tatsuo Takaori, Toru Hosoya, Akiko Tezuka, Hiroyuki Nagase, Shotaro Ishihara, Takuma Kadoshima, Taisuke Muguruma, Keiko Ishigaki, Keiko Sakurai, Hidetoshi Mizoguchi, Akira Novitch, Bennett G. Toda, Tatsushi Watanabe, Momoko Aoi, Takashi |
author_facet | Taniguchi-Ikeda, Mariko Koyanagi-Aoi, Michiyo Maruyama, Tatsuo Takaori, Toru Hosoya, Akiko Tezuka, Hiroyuki Nagase, Shotaro Ishihara, Takuma Kadoshima, Taisuke Muguruma, Keiko Ishigaki, Keiko Sakurai, Hidetoshi Mizoguchi, Akira Novitch, Bennett G. Toda, Tatsushi Watanabe, Momoko Aoi, Takashi |
author_sort | Taniguchi-Ikeda, Mariko |
collection | PubMed |
description | Fukuyama congenital muscular dystrophy (FCMD) is a severe, intractable genetic disease that affects the skeletal muscle, eyes, and brain and is attributed to a defect in alpha dystroglycan (αDG) O-mannosyl glycosylation. We previously established disease models of FCMD; however, they did not fully recapitulate the phenotypes observed in human patients. In this study, we generated induced pluripotent stem cells (iPSCs) from a human FCMD patient and differentiated these cells into three-dimensional brain organoids and skeletal muscle. The brain organoids successfully mimicked patient phenotypes not reliably reproduced by existing models, including decreased αDG glycosylation and abnormal radial glial (RG) fiber migration. The basic polycyclic compound Mannan-007 (Mn007) restored αDG glycosylation in the brain and muscle models tested and partially rescued the abnormal RG fiber migration observed in cortical organoids. Therefore, our study underscores the importance of αDG O-mannosyl glycans for normal RG fiber architecture and proper neuronal migration in corticogenesis. |
format | Online Article Text |
id | pubmed-8487058 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-84870582021-10-07 Restoration of the defect in radial glial fiber migration and cortical plate organization in a brain organoid model of Fukuyama muscular dystrophy Taniguchi-Ikeda, Mariko Koyanagi-Aoi, Michiyo Maruyama, Tatsuo Takaori, Toru Hosoya, Akiko Tezuka, Hiroyuki Nagase, Shotaro Ishihara, Takuma Kadoshima, Taisuke Muguruma, Keiko Ishigaki, Keiko Sakurai, Hidetoshi Mizoguchi, Akira Novitch, Bennett G. Toda, Tatsushi Watanabe, Momoko Aoi, Takashi iScience Article Fukuyama congenital muscular dystrophy (FCMD) is a severe, intractable genetic disease that affects the skeletal muscle, eyes, and brain and is attributed to a defect in alpha dystroglycan (αDG) O-mannosyl glycosylation. We previously established disease models of FCMD; however, they did not fully recapitulate the phenotypes observed in human patients. In this study, we generated induced pluripotent stem cells (iPSCs) from a human FCMD patient and differentiated these cells into three-dimensional brain organoids and skeletal muscle. The brain organoids successfully mimicked patient phenotypes not reliably reproduced by existing models, including decreased αDG glycosylation and abnormal radial glial (RG) fiber migration. The basic polycyclic compound Mannan-007 (Mn007) restored αDG glycosylation in the brain and muscle models tested and partially rescued the abnormal RG fiber migration observed in cortical organoids. Therefore, our study underscores the importance of αDG O-mannosyl glycans for normal RG fiber architecture and proper neuronal migration in corticogenesis. Elsevier 2021-09-17 /pmc/articles/PMC8487058/ /pubmed/34632335 http://dx.doi.org/10.1016/j.isci.2021.103140 Text en © 2021 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Taniguchi-Ikeda, Mariko Koyanagi-Aoi, Michiyo Maruyama, Tatsuo Takaori, Toru Hosoya, Akiko Tezuka, Hiroyuki Nagase, Shotaro Ishihara, Takuma Kadoshima, Taisuke Muguruma, Keiko Ishigaki, Keiko Sakurai, Hidetoshi Mizoguchi, Akira Novitch, Bennett G. Toda, Tatsushi Watanabe, Momoko Aoi, Takashi Restoration of the defect in radial glial fiber migration and cortical plate organization in a brain organoid model of Fukuyama muscular dystrophy |
title | Restoration of the defect in radial glial fiber migration and cortical plate organization in a brain organoid model of Fukuyama muscular dystrophy |
title_full | Restoration of the defect in radial glial fiber migration and cortical plate organization in a brain organoid model of Fukuyama muscular dystrophy |
title_fullStr | Restoration of the defect in radial glial fiber migration and cortical plate organization in a brain organoid model of Fukuyama muscular dystrophy |
title_full_unstemmed | Restoration of the defect in radial glial fiber migration and cortical plate organization in a brain organoid model of Fukuyama muscular dystrophy |
title_short | Restoration of the defect in radial glial fiber migration and cortical plate organization in a brain organoid model of Fukuyama muscular dystrophy |
title_sort | restoration of the defect in radial glial fiber migration and cortical plate organization in a brain organoid model of fukuyama muscular dystrophy |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487058/ https://www.ncbi.nlm.nih.gov/pubmed/34632335 http://dx.doi.org/10.1016/j.isci.2021.103140 |
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