Axonal Ensheathment in the Nervous System of Lamprey: Implications for the Evolution of Myelinating Glia

Abstract

In the nervous system, myelination of axons enables rapid impulse conduction and is a specialized function of glial cells. Myelinating glia are the last cell type to emerge in the evolution of vertebrate nervous systems, presumably in ancient jawed vertebrates (gnathostomata) because jawless vertebrates (agnathans) lack myelin. We have hypothesized that, in these unmyelinated species, evolutionary progenitors of myelinating cells must have existed that should still be present in contemporary agnathan species. Here, we used advanced electron microscopic techniques to reveal axon-glia interactions in the sea lamprey Petromyzon marinus. By quantitative assessment of the spinal cord and the peripheral lateral line nerve, we observed a marked maturation-dependent growth of axonal calibers. In peripheral nerves, all axons are ensheathed by glial cells either in bundles or, when larger than the threshold caliber of 3 m, individually. The ensheathing glia are covered by a basal lamina and express SoxE-transcription factors, features of mammalian Remak-type Schwann cells. In larval lamprey, the ensheathment of peripheral axons leaves gaps that are closed in adults. CNS axons are also covered to a considerable extent by glial processes, which contain a high density of intermediate filaments, glycogen particles, large lipid droplets, and desmosomes, similar to mammalian astrocytes. Indeed, by in situ hybridization, these glial cells express the astrocyte marker Aldh1l1. Specimens were of unknown sex. Our observations imply that radial sorting, ensheathment, and presumably also metabolic support of axons are ancient functions of glial cells that predate the evolutionary emergence of myelin in jawed vertebrates.

Structural myelin defects are associated with low axonal ATP levels but rapid recovery from energy deprivation in a mouse model of spastic paraplegia

“…The CAP, elicited by the maximum stimulation of 0.75 mA, was recorded at baseline stimulation frequency at 0.1 Hz. During high frequency stimulation, nerves were stimulated by pulses of increasing frequency (1,4,7,15,25,50,75, 100 Hz) each applied for 30 s (ramp protocol).…”

Metabolic Interaction Between Schwann Cells and Axons Under Physiological and Disease Conditions

“…The development of such cells precedes the emergence of structured myelin by several million years (Bullock et al, 1984) and suggests that myelin-independent axonal support might be the primary function of glia. In the lamprey peripheral lateral line nerve, glial cells similar to SC engulf multiple small-caliber axons in structures reminiscent of Remak bundles and sort out larger caliber axons (greater than 3 µm) into one-toone structures (Weil et al, 2018). These cells express SoxE genes such as SoxE2 and SoxE3, which are equivalent to mammalian SC-specific Sox10 and Sox9, respectively, suggesting that they are orthologous to SC.…”

White matter integrity requires continuous myelin synthesis at the inner tongue

“…FIB-SEM was performed as described in (Steyer et al, 2019b, Weil et al, 2018. To visualize the emergence of membrane structures along a myelinated internode we imaged optic nerves 16 weeks and 26 weeks after tamoxifen induction.…”