Oligodendrocyte calcium signaling sculpts myelin sheath morphology. Iyer, M., Kantarci, H., Ambiel, N., Novak, S. W., Andrade, L. R., Lam, M., Münch, A. E., Yu, X., Khakh, B. S., Manor, U., & Zuchero, J. B. bioRxiv, Cold Spring Harbor Laboratory, 2023. ![Oligodendrocyte calcium signaling sculpts myelin sheath morphology [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex Myelin is essential for rapid nerve signaling and is increasingly found to play important roles in learning and in diverse diseases of the CNS. Morphological parameters of myelin such as sheath length and thickness are regulated by neuronal activity and can precisely tune conduction velocity, but the mechanisms controlling sheath morphology are poorly understood. Local calcium signaling has been observed in nascent myelin sheaths and can be modulated by neuronal activity. However, the role of calcium signaling in sheath formation and remodeling is unknown. Here, we used genetic tools to attenuate oligodendrocyte calcium signaling during active myelination in the developing mouse CNS. Surprisingly, we found that genetic calcium attenuation did not grossly affect the number of myelinated axons or myelin thickness. Instead, calcium attenuation caused striking myelination defects resulting in shorter, dysmorphic sheaths. Mechanistically, calcium attenuation reduced actin filaments in oligodendrocytes, and an intact actin cytoskeleton was necessary and sufficient to achieve accurate myelin morphology. Together, our work reveals a novel cellular mechanism required for accurate CNS myelin formation and provides mechanistic insight into how oligodendrocytes may respond to neuronal activity to sculpt myelin sheaths throughout the nervous system.Competing Interest StatementThe authors have declared no competing interest.
@article {Iyer2023.04.11.536299,
author = {Manasi Iyer and Husniye Kantarci and Nicholas Ambiel and Sammy W. Novak and Leonardo R. Andrade and Mable Lam and Alexandra E. M{\"u}nch and Xinzhu Yu and Baljit S. Khakh and Uri Manor and J. Bradley Zuchero},
title = {Oligodendrocyte calcium signaling sculpts myelin sheath morphology},
elocation-id = {2023.04.11.536299},
year = {2023},
doi = {10.1101/2023.04.11.536299},
publisher = {Cold Spring Harbor Laboratory},
abstract = {Myelin is essential for rapid nerve signaling and is increasingly found to play important roles in learning and in diverse diseases of the CNS. Morphological parameters of myelin such as sheath length and thickness are regulated by neuronal activity and can precisely tune conduction velocity, but the mechanisms controlling sheath morphology are poorly understood. Local calcium signaling has been observed in nascent myelin sheaths and can be modulated by neuronal activity. However, the role of calcium signaling in sheath formation and remodeling is unknown. Here, we used genetic tools to attenuate oligodendrocyte calcium signaling during active myelination in the developing mouse CNS. Surprisingly, we found that genetic calcium attenuation did not grossly affect the number of myelinated axons or myelin thickness. Instead, calcium attenuation caused striking myelination defects resulting in shorter, dysmorphic sheaths. Mechanistically, calcium attenuation reduced actin filaments in oligodendrocytes, and an intact actin cytoskeleton was necessary and sufficient to achieve accurate myelin morphology. Together, our work reveals a novel cellular mechanism required for accurate CNS myelin formation and provides mechanistic insight into how oligodendrocytes may respond to neuronal activity to sculpt myelin sheaths throughout the nervous system.Competing Interest StatementThe authors have declared no competing interest.},
URL = {https://www.biorxiv.org/content/early/2023/04/12/2023.04.11.536299},
eprint = {https://www.biorxiv.org/content/early/2023/04/12/2023.04.11.536299.full.pdf},
journal = {bioRxiv}
}
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B."],"bibdata":{"bibtype":"article","type":"article","author":[{"firstnames":["Manasi"],"propositions":[],"lastnames":["Iyer"],"suffixes":[]},{"firstnames":["Husniye"],"propositions":[],"lastnames":["Kantarci"],"suffixes":[]},{"firstnames":["Nicholas"],"propositions":[],"lastnames":["Ambiel"],"suffixes":[]},{"firstnames":["Sammy","W."],"propositions":[],"lastnames":["Novak"],"suffixes":[]},{"firstnames":["Leonardo","R."],"propositions":[],"lastnames":["Andrade"],"suffixes":[]},{"firstnames":["Mable"],"propositions":[],"lastnames":["Lam"],"suffixes":[]},{"firstnames":["Alexandra","E."],"propositions":[],"lastnames":["Münch"],"suffixes":[]},{"firstnames":["Xinzhu"],"propositions":[],"lastnames":["Yu"],"suffixes":[]},{"firstnames":["Baljit","S."],"propositions":[],"lastnames":["Khakh"],"suffixes":[]},{"firstnames":["Uri"],"propositions":[],"lastnames":["Manor"],"suffixes":[]},{"firstnames":["J.","Bradley"],"propositions":[],"lastnames":["Zuchero"],"suffixes":[]}],"title":"Oligodendrocyte calcium signaling sculpts myelin sheath morphology","elocation-id":"2023.04.11.536299","year":"2023","doi":"10.1101/2023.04.11.536299","publisher":"Cold Spring Harbor Laboratory","abstract":"Myelin is essential for rapid nerve signaling and is increasingly found to play important roles in learning and in diverse diseases of the CNS. Morphological parameters of myelin such as sheath length and thickness are regulated by neuronal activity and can precisely tune conduction velocity, but the mechanisms controlling sheath morphology are poorly understood. Local calcium signaling has been observed in nascent myelin sheaths and can be modulated by neuronal activity. However, the role of calcium signaling in sheath formation and remodeling is unknown. Here, we used genetic tools to attenuate oligodendrocyte calcium signaling during active myelination in the developing mouse CNS. Surprisingly, we found that genetic calcium attenuation did not grossly affect the number of myelinated axons or myelin thickness. Instead, calcium attenuation caused striking myelination defects resulting in shorter, dysmorphic sheaths. Mechanistically, calcium attenuation reduced actin filaments in oligodendrocytes, and an intact actin cytoskeleton was necessary and sufficient to achieve accurate myelin morphology. 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