MBNL-dependent impaired development connectivity within neuromuscular circuits in myotonic dystrophy type 1
| Autor: | Tahraoui-Bories, Julie, Mérien, Antoine, Roussange, Florine, González-Barriga, Anchel, Lainé, Jeanne, Leteur, Céline, Polvèche, Hélène, Polentes, Jérome, Carteron, Alexandre, Jarrige, Margot, Gomes-Pereira, Mário, Furling, Denis, Martinat, Cécile |
|---|---|
| Přispěvatelé: | Institut des cellules souches pour le traitement et l'étude des maladies monogéniques (I-STEM), Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Généthon, Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU) |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
iPSC
[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics Myotonic dystrophy type 1 RNA biology Trinucleotide repeat expansion Neuromuscular junction [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology [SDV.BC]Life Sciences [q-bio]/Cellular Biology [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology |
| Zdroj: | International Myotonic Dystrophy Consortium Meeting International Myotonic Dystrophy Consortium Meeting, Jun 2022, Osaka, Japan |
| Popis: | International audience; Introduction: Myotonic dystrophy type I (DM1) is one the most frequent muscular dystrophy in adults. Although DM1 has long been considered mainly as a muscle disorder, growing evidence suggests the involvement in peripheral nerves in the pathogenicity of DM1 raising the question whether motoneurons actively contribute to neuromuscular defects in DM1.Methods: By using a micropatterned 96-well plate as a co-culture platform, we generated a functional humanized cellular model combining DM1 hiPSC-derived MNs and healthy skeletal muscle cells.Results: Such approaches led to the identification of pre-synaptic defects which affect development or stability of the neuromuscular junction at an early developmental stage. These neuropathological defects could be reproduced by the loss of RNA-binding MBNL proteins, whose loss of function is associated with muscular defects associated with DM1.Conclusions: These experiments suggested that the functional defects associated to MNs can be directly attributed to the MBNL family proteins. Altogether, these findings hold several new implications for DM1 pathogenesis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|