Myelin sheath lengths in the central nervous system scale to axon diameter via oligodendroglial Piezo1
- 1Department of Cell and Developmental Biology, SUNY Upstate Medical University, Syracuse, New York, United States of America
- 2Department of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, New York, United States of America
Abstract
Myelin sheath lengths vary by an order of magnitude in the central nervous system (CNS) and tune the timing of neuronal signaling. Thus, variation in myelin sheath length has been proposed to coordinate the timing of neuronal signaling to ultimately impact behavior. The mechanisms to establish myelin sheath length are unknown. For decades, reports have documented that in vivo myelin sheath size scales with the diameter of the ensheathed axon. We previously demonstrated diameter is sufficient to instruct myelin sheath lengths formed by rat oligodendrocytes using a synthetic axon culture system. The mechanisms of oligodendrocyte diameter-sensing and its translation into sheath elongation are still unknown. Here, we demonstrate that diameter-sensing and sheath length is locally regulated: each individual myelin sheath responds to the underlying fiber diameter. We uncover a novel mechanism for scaling myelin sheath length to fiber diameter, through mechanosensitive ion channel Piezo1. In mice in vivo, Piezo1 impacts the elongation of myelin sheaths on large diameter axons, recapitulating our in vitro results. Yet, surprisingly, there is no impact on myelin thickness with conditional Piezo1 loss. We propose Piezo1 provides a mechanism to establish hard-wired myelin sheath patterns, where oligodendrocytes transduce axon diameter into generating myelin segments with vastly different lengths.
How oligodendrocytes match their myelin production to the scale of the axon they ensheathe is poorly understood. This study shows that oligodendrocytes require Piezo1 to appropriately scale sheath lengths to axon diameter, supporting the temporal coordination of neuronal signaling.
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BibTeX
@article{young2026myelin,
title = {{Myelin sheath lengths in the central nervous system scale to axon diameter via oligodendroglial Piezo1}},
author = {Amanda R. Young and Ashley Galfano and Jacob Reyngoudt and Ryan W. Lewis and Martha Cash and Beckam Polis and Myah Zalusky and Avipsha Datta and Marie E. Bechler},
journal = {PLOS Biology},
year = {2026},
month = sep,
doi = {10.1371/journal.pbio.3003992},
url = {https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3003992},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Myelin sheath lengths in the central nervous system scale to axon diameter via oligodendroglial Piezo1
AU - Amanda R. Young
AU - Ashley Galfano
AU - Jacob Reyngoudt
AU - Ryan W. Lewis
AU - Martha Cash
AU - Beckam Polis
AU - Myah Zalusky
AU - Avipsha Datta
AU - Marie E. Bechler
PY - 2026
DA - 2026/09/21
JO - PLOS Biology
DO - 10.1371/journal.pbio.3003992
UR - https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3003992
AB - Myelin sheath lengths vary by an order of magnitude in the central nervous system (CNS) and tune the timing of neuronal signaling. Thus, variation in myelin sheath length has been proposed to coordinate the timing of neuronal signaling to ultimately impact behavior. The mechanisms to establish myelin sheath length are unknown. For decades, reports have documented that in vivo myelin sheath size scales with the diameter of the ensheathed axon. We previously demonstrated diameter is sufficient to instruct myelin sheath lengths formed by rat oligodendrocytes using a synthetic axon culture system. The mechanisms of oligodendrocyte diameter-sensing and its translation into sheath elongation are still unknown. Here, we demonstrate that diameter-sensing and sheath length is locally regulated: each individual myelin sheath responds to the underlying fiber diameter. We uncover a novel mechanism for scaling myelin sheath length to fiber diameter, through mechanosensitive ion channel Piezo1. In mice in vivo, Piezo1 impacts the elongation of myelin sheaths on large diameter axons, recapitulating our in vitro results. Yet, surprisingly, there is no impact on myelin thickness with conditional Piezo1 loss. We propose Piezo1 provides a mechanism to establish hard-wired myelin sheath patterns, where oligodendrocytes transduce axon diameter into generating myelin segments with vastly different lengths. How oligodendrocytes match their myelin production to the scale of the axon they ensheathe is poorly understood. This study shows that oligodendrocytes require Piezo1 to appropriately scale sheath lengths to axon diameter, supporting the temporal coordination of neuronal signaling.
SN - 1545-7885
ER -