Development of myelinating glia: An overview

Abstract

Myelin is essential to nervous system function, playing roles in saltatory conduction and trophic support. Oligodendrocytes (OLs) and Schwann cells (SCs) form myelin in the central and peripheral nervous systems respectively and follow different developmental paths. OLs are neural stem-cell derived and follow an intrinsic developmental program resulting in a largely irreversible differentiation state. During embryonic development, OL precursor cells (OPCs) are produced in distinct waves originating from different locations in the central nervous system, with a subset developing into myelinating OLs. OPCs remain evenly distributed throughout life, providing a population of responsive, multifunctional cells with the capacity to remyelinate after injury. SCs derive from the neural crest, are highly dependent on extrinsic signals, and have plastic differentiation states. SC precursors (SCPs) are produced in early embryonic nerve structures and differentiate into multipotent immature SCs (iSCs), which initiate radial sorting and differentiate into myelinating and non-myelinating SCs. Differentiated SCs retain the capacity to radically change phenotypes in response to external signals, including becoming repair SCs, which drive peripheral regeneration. While several

RNF220-mediated K63-linked polyubiquitination stabilizes Olig proteins during oligodendroglial development and myelination

“…S4E). It is known that there is a chronological procedure of olilgodendrolial development in postnatal mouse brains: before P7 OPCs are mainly proliferated and after that OL cells are differentiated ( 20 ). Therefore, to examine whether the impaired OL differentiation after RNF220 depletion is a secondary effect to the early deregulated proliferation, RNF220 flox/flox mice were crossed with the PDGFR α -CreER transgenic mouse line, an OPC-specific tamoxifen-inducible Cre line ( 21 ), to obtain the three mouse lines ( RNF220 wt/wt ;PDGFR α -CreER, RNF220-iWT ; RNF220 flox/wt ;PDGFRα-CreER, RNF220-icHet ; RNF220 flox/flox ;PDGFRα-CreER, RNF220-icKO ).…”

“…The Morris water maze test was used to examine spatial learning and memory, and it was found that RNF220-cKO mice took more time to find the hidden platform on the second to sixth days during the 8-day training (escape latency: day 1: WT: 57. 20 3D), suggesting a higher escape latency and impairment of spatial learning. One day after the training trails, spatial memory was tested and it was shown that the total movement distance of RNF220-cKO mice was not shorter, even longer, than the RNF220-WT or RNF220-cHet control mice (WT: 534.20 ± 131.90 cm; cHet: 590.70 ± 184.00 cm; cKO: 711.30 ± 101.50 cm; Fig.…”

The stability of the myelinating oligodendrocyte transcriptome is regulated by the nuclear lamina

“…These differences could be attributed to the unique functional features of the two myelinating cell types, with oligodendrocytes being post-mitotic stationary cells 5 with a very stable transcriptome and the ability to wrap multiple axons with their myelin membrane and Schwann cells being more plastic, wrapping a single axon and retaining the ability to dedifferentiate and migrate in response to injury. 82 , 83 Differences could also be related to the distinct expression patterns of the nuclear lamins detected in the two cell types. Although both oligodendrocytes and Schwann cells express LMNA/C, only central myelinating glia display a characteristic inverse relationship with LMNB1 levels, while Schwann cells have constant levels of both lamins regardless of whether they are proliferating or differentiating.…”

Early cortical oligodendrocyte precursor cells are transcriptionally distinct and lack synaptic connections

“…The cluster "OPC1a, OPC1b" and "OPCmit" were also well aligned with our E16.5 data set and we assumed that those cells represented OPCs from brain regions which at E16.5 contain OPCs which already had developed further and established synapses. For example, in cerebellum and spinal cord, regions at least partially contained in our samples, OPCs start to differentiate around birth whereas differentiation only occurs approximately 1 week later in the rodent cortex (Cristobal & Lee, 2022;Reynolds & Wilkin, 1988;Trapp et al, 1997).…”