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1559-11826252025MayMolecular neurobiologyMol NeurobiolCharacterization of Dystrophin Dp71 Expression and Interaction Partners in Embryonic Brain Development: Implications for Duchenne/Becker Muscular Dystrophy.625662726256-627210.1007/s12035-024-04676-6Duchenne/Becker muscular dystrophy (DMD/BMD) manifests progressive muscular dystrophy and non-progressive central nervous disorder. The neural disorder is possibly caused by abnormalities in the developmental period; however, basic research to understand the mechanisms remains underdeveloped. The responsible gene, Dmd (dystrophin), generates multiple products derived from several gene promoters. Here, we aim to characterize the expression of the shortest product, Dp71, during embryonic brain development and to identify its interaction proteins by using Dp71-specific tag-insertion mice. We showed that Dp71 and Dp140 were major dystrophin products significantly detectable in the mouse embryonic brains and Dp71 was the only dystrophin product derived from intron-62 gene promoter in the physiological mouse brains. Although both Dp71f (exon 78-exclusive form) and Dp71d (exon 78-inclusive form) existed in the embryonic brains, Dp71f and Dp71d were dominant forms in the prenatal and postnatal periods, respectively. We histologically found that Dp71 was prominently expressed in the neuroepithelium of the dorsal and medial telencephalon, which gives rise to the primordial cerebral cortex and hippocampus. Deeper analysis using in vitro primary culture verified Dp71 expressions in Nestin-positive neural stem/progenitor, Fabp7-positive radial glia, and Gfap-positive astrocytic cell populations. Interestingly, Dp71 was downregulated upon neuronal differentiation from stem/progenitor cells into TuJ1-positive immature neurons; however, Dp71 became detectable at Gephyrin-positive inhibitory postsynapses within mature neurons. Importantly, interactome analysis revealed dystroglycan, dystrobrevins, and syntrophins as dominant Dp71-partners in the embryonic neural stem/progenitor cells. Thus, the presence of Dp71-dystroglycan macromolecular complex was clearly established at an early stage of embryonic brain development, which sheds light on relations between fetal abnormalities and intellectual disabilities in DMD/BMD.© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.FujimotoTakahiroTDepartment of Pathology and Applied Neurobiology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, 465 Kajii-Cho, Kawaramachi Hirokoji, Kamigyo-Ku, Kyoto, 602-8566, Japan. tfuji@koto.kpu-m.ac.jp.MoriMiyukiMDepartment of Pathology and Applied Neurobiology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, 465 Kajii-Cho, Kawaramachi Hirokoji, Kamigyo-Ku, Kyoto, 602-8566, Japan.TonosakiMadokaMDepartment of Pathology and Applied Neurobiology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, 465 Kajii-Cho, Kawaramachi Hirokoji, Kamigyo-Ku, Kyoto, 602-8566, Japan.YaoiTakeshiTDepartment of Pathology and Applied Neurobiology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, 465 Kajii-Cho, Kawaramachi Hirokoji, Kamigyo-Ku, Kyoto, 602-8566, Japan.NakanoKentaKDepartment of Laboratory Animal Medicine, Research Institute, National Center for Global Health and Medicine (NCGM), Tokyo, 162-8655, Japan.OkamuraTadashiTDepartment of Laboratory Animal Medicine, Research Institute, National Center for Global Health and Medicine (NCGM), Tokyo, 162-8655, Japan.ItohKyokoKDepartment of Pathology and Applied Neurobiology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, 465 Kajii-Cho, Kawaramachi Hirokoji, Kamigyo-Ku, Kyoto, 602-8566, Japan.eng18K07883Grants-in-Aid for Scientific Research (Kakenhi)(5-7)Intramural Research Grant for Neurological and Psychiatric Disorders of NCNP20A1019Grants-in-Aid for Research from the National Center for Global Health and MedicineJournal Article20250106
United StatesMol Neurobiol89009630893-76480Dystrophin0apo-dystrophin 1IMAnimalsDystrophinmetabolismgeneticsBrainembryologymetabolismMuscular Dystrophy, DuchennemetabolismgeneticsembryologypathologyMiceGene Expression Regulation, DevelopmentalMice, Inbred C57BLBrain development,Dp71,Duchenne muscular dystrophyDystrophin,Neural stem cells,Declarations. Ethics Approval and Consent to Participate: All animal experiments were approved by the President of Kyoto Prefectural University of Medicine and the National Center for Global Health and Medicine following consideration by the Institutional Animal Care and Use Committee of each institute (approval ID: M2020-241–1, M2021-268, M2022-254, M2023-546, M2024-223 and 18037) and were carried out in accordance with institutional procedures, national guidelines, and the relevant national laws on the protection of animals. The welfare of animals was considered during experiments. Consent for Publication: Not applicable. 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