Individual axons regulate the myelinating potential of single oligodendrocytes in vivo

Abstract

SUMMARYThe majority of axons in the central nervous system (CNS) are eventually myelinated by oligodendrocytes, but whether the timing and extent of myelination in vivo reflect intrinsic properties of oligodendrocytes, or are regulated by axons, remains undetermined. Here, we use zebrafish to study CNS myelination at single-cell resolution in vivo. We show that the large caliber Mauthner axon is the first to be myelinated (shortly before axons of smaller caliber) and that the presence of supernumerary large caliber Mauthner axons can profoundly affect myelination by single oligodendrocytes. Oligodendrocytes that typically myelinate just one Mauthner axon in wild type can myelinate multiple supernumerary Mauthner axons. Furthermore, oligodendrocytes that exclusively myelinate numerous smaller caliber axons in wild type can readily myelinate small caliber axons in addition to the much larger caliber supernumerary Mauthner axons. These data indicate that single oligodendrocytes can myelinate diverse axons and that their myelinating potential is actively regulated by individual axons.

Integrin-Linked Kinase Regulates Process Extension in Oligodendrocytes via Control of Actin Cytoskeletal Dynamics

“…With regard to the former, OL morphological complexity is negatively correlated with the diameter of the axon(s) it myelinates. Individual OLs will either myelinate a large number of small axons or a small number of large axons (Butt and Berry, 2000;Almeida et al, 2011). Thus, following ILK loss, we would expect exacerbation of small axon amyelination as a result of the OL's inability to generate a high number of processes.…”

“…First, the myelination potential of any single OL is dependent on its ability to compete with neighboring OLs for axonal space (Chong et al, 2012). Second, OLs are plastic, able to form myelin beyond what a permissive environment would normally allow (Almeida et al, 2011;Chong et al, 2012). It is therefore reasonable to postulate compensation as occurring through endogenous "WT" OLs, an intriguing possibility when considering future development of demyelinating disease therapies.…”

Developmental pruning of early-stage myelin segments during CNS myelination in vivo

“…In the spinal cord of zebrafish, the Mauthner ("M") cell axon, the largest one in the animal, is the first to be myelinated [4]. Some OLs initially formed myelin segments on both Maxons and other small axons ( Figure 1F and Supplementary information, Figure S3).…”

“…Furthermore, segments wrapping larger axons will win and ones wrapping smaller axons will lose, raising the possibility that myelin pruning exhibits a competitive property. This may explain why large axons recruit glial wrapping early and receive more myelin layers than small axons [1,4,10]. During the pruning process, NRG-ErbB signaling may serve as a competitive signal at extending myelin segments or a pruning signal at pruning segments.…”

Nonlinear light-sheet fluorescence microscopy by photobleaching imprinting

“…The sample was excited by a 532 nm continuous wave (CW) laser and imaged on Next, we imaged a zebrafish embryo 6 days postfertilization (dpf ) in vivo with LSF -PIM. In the transgenic embryo, the myelin basic protein (mbp) promoter drives expression of mcherry throughout the nervous system [12,13], and the spinal cord was imaged. The light sheet's incident direction (green arrow) was perpendicular to the spinal cord axis (figure 4a).…”