Restoration of the defect in radial glial fiber migration and cortical plate organization in a brain organoid model of Fukuyama muscular dystrophy

Mariko Taniguchi-Ikeda, Michiyo Koyanagi-Aoi, Tatsuo Maruyama, Toru Takaori, Akiko Hosoya, Hiroyuki Tezuka, Shotaro Nagase, Takuma Ishihara, Taisuke Kadoshima, Keiko Muguruma, Keiko Ishigaki, Hidetoshi Sakurai, Akira Mizoguchi, Bennett G. Novitch, Tatsushi Toda, Momoko Watanabe, Takashi Aoi

研究成果: ジャーナルへの寄稿学術論文査読

4 被引用数 (Scopus)

抄録

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.

本文言語英語
論文番号103140
ジャーナルiScience
24
10
DOI
出版ステータス出版済み - 22-10-2021

All Science Journal Classification (ASJC) codes

  • 一般

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