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Review
. 2022 Sep 6:10:952135.
doi: 10.3389/fcell.2022.952135. eCollection 2022.

The molecular regulation of oligodendrocyte development and CNS myelination by ECM proteins

Momona Yamada  1 , Miho Iwase  1 , Binri Sasaki  1 , Nobuharu Suzuki  1
Affiliations
Review

The molecular regulation of oligodendrocyte development and CNS myelination by ECM proteins

Momona Yamada et al. Front Cell Dev Biol. .

Abstract

Oligodendrocytes are myelin-forming cells in the central nervous system (CNS). The development of oligodendrocytes is regulated by a large number of molecules, including extracellular matrix (ECM) proteins that are relatively less characterized. Here, we review the molecular functions of the major ECM proteins in oligodendrocyte development and pathology. Among the ECM proteins, laminins are positive regulators in oligodendrocyte survival, differentiation, and/or myelination in the CNS. Conversely, fibronectin, tenascin-C, hyaluronan, and chondroitin sulfate proteoglycans suppress the differentiation and myelination. Tenascin-R shows either positive or negative functions in these activities. In addition, the extracellular domain of the transmembrane protein teneurin-4, which possesses the sequence homology with tenascins, promotes the differentiation of oligodendrocytes. The activities of these ECM proteins are exerted through binding to the cellular receptors and co-receptors, such as integrins and growth factor receptors, which induces the signaling to form the elaborated and functional structure of myelin. Further, the ECM proteins dynamically change their structures and functions at the pathological conditions as multiple sclerosis. The ECM proteins are a critical player to serve as a component of the microenvironment for oligodendrocytes in their development and pathology.

Keywords: chondroitin sulfate proteoglycan; extracellular matrix; fibronectin; hyaluronan; laminin; myelin; oligodendrocyte; tenascin.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
The functions of ECM molecules through cellular receptors. Laminins expressed in vascular basement membrane or along axons promote survival and differentiation of oligodendrocytes (OLs) and myelination via integrins in coordination with growth factor receptors (GFRs). Chondroitin sulfate proteoglycans (CSPGs) form aggregates and inhibit the laminin-integrin signaling. The cleavage of dystroglycan downstream of the binding to laminin induce OL precursor cell (OPC) proliferation. OL differentiation and myelination by the laminin-dystroglycan binding is enhanced when dystroglycan interacts with the complex of insulin-like growth factor (IGF1) and IGF receptor (IGFR). Tenascin-R and teneurin-4 promotes differentiation of OLs while tenascin-C inhibits it via the interaction of integrins with contactin-1. Fibronectin aggregation secreted by activated astrocytes negatively regulates OL differentiation. Also, hyaluronan inhibits OL differentiation through the TLR2 signaling.
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