Rio-Hortega's drawings revisited with fluorescent proteins define a cytoplasm filled channel system of CNS myelin

Edgar, J. M. , McGowan, E., Chapple, K., Möbius, W., Lemgruber, L. , Insall, R. H. , Nave, K.-A. and Boullerne, A. (2021) Rio-Hortega's drawings revisited with fluorescent proteins define a cytoplasm filled channel system of CNS myelin. Journal of Anatomy, 239(6), pp. 1241-1255. (doi: 10.1111/joa.13577)

Abstract

A century ago this year, Pío del Río-Hortega (1921) coined the term ‘oligodendroglia’ for the ‘interfascicular glia’ with very few processes, launching an extensive discovery effort on his new cell type. One hundred years later, we review his original contributions to our understanding of the system of cytoplasmic channels within myelin in the context of what we observe today using light and electron microscopy of genetically encoded fluorescent reporters and immunostaining. We use the term myelinic channel system to describe the cytoplasm-delimited spaces associated with myelin; being the paranodal loops, inner and outer tongues, cytoplasm-filled spaces through compact myelin and further complex motifs associated to the sheath. Using a central nervous system myelinating cell culture model that contains all major neural cell types and produces compact myelin, we find that td-tomato fluorescent protein delineates the myelinic channel system in a manner reminiscent of the drawings of adult white matter by Río-Hortega, despite that he questioned whether some cytoplasmic figures he observed represented artefact. Together, these data lead us to propose a slightly revised model of the ‘unrolled’ sheath. Further, we show that the myelinic channel system, while relatively stable, can undergo subtle dynamic shape changes over days. Importantly, we capture an under-appreciated complexity of the myelinic channel system in mature myelin sheaths.

• Item Type: Articles
• Additional Information: Funding information: UK MS Society, Grant/Award Number: 38 and 127; NIH/National Library of Medicine, Grant/Award Number: G13LM011465; Deutsche Forschungsgemeinschaft, Grant/Award Number: TRR 274/1 2020—408885537; Research Center Nanoscale Microscopy and Molecular Physiology of the Brain; ERC Advanced Grants AxoGlia and MyeliNANO.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Insall, Professor Robert and Edgar, Professor Julia and Chapple, Dr Katie and Lemgruber Soares, Dr Leandro
• Authors: Edgar, J. M., McGowan, E., Chapple, K., Möbius, W., Lemgruber, L., Insall, R. H., Nave, K.-A., and Boullerne, A.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Research Centre: College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology
• Journal Name: Journal of Anatomy
• Publisher: Wiley
• ISSN: 0021-8782
• ISSN (Online): 1469-7580
• Published Online: 28 October 2021
• Copyright Holders: Copyright © 2021 The Authors
• First Published: First published in Journal of Anatomy 239(6): 1241-1255
• Publisher Policy: Reproduced under a Creative Commons Licence