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Myelin sheath lengths in the central nervous system scale to axon diameter via oligodendroglial Piezo1
Myelin sheath lengths vary by an order of magnitude in the central nervous system and tune the timing of neuronal signaling. Variation in myelin sheath length has therefore been proposed to coordinate the timing of neuronal signaling to ultimately impact behavior. For decades, reports have documented that in vivo myelin sheath size scales with the diameter of the ensheathed axon, but the mechanisms of oligodendrocyte diameter-sensing and its translation into sheath elongation are still unknown. Young et al. demonstrate that diameter-sensing and sheath length are locally regulated: each individual myelin sheath responds to the underlying fiber diameter via the mechanosensitive ion channel Piezo1. In mice in vivo, Piezo1 impacts the elongation of myelin sheaths on large diameter axons, recapitulating the in vitro results. Yet, surprisingly, conditional Piezo1 loss does not impact myelin thickness. The authors propose that Piezo1 provides a mechanism to establish hard-wired myelin sheath patterns, whereby oligodendrocytes transduce axon diameter into generating myelin segments with vastly different lengths. The image shows a single oligodendrocyte cell myelinating mixed diameter synthetic axons. A myelin basic protein immunofluorescence image has been colorized according to confocal z-plane and modified with edge detection to highlight numerous myelin sheaths of different lengths formed by a single oligodendrocyte. The longer myelin sheath formed on a larger diameter synthetic axon stands out in blue-green.
Image Credit: Marie E. Bechler