Abstract
In the developing central nervous system (CNS), oligodendrocyte precursor cells (OPCs) migrate along blood vessels and are widely distributed in the CNS. Meanwhile, OPCs require survival factors from the extracellular microenvironment. In other tissues, laminins, heterotrimetric (αβγ) extracellular matrix proteins, promote cell migration and survival. However, the expression pattern and functions of laminins in OPC development remain poorly understood. In the present study, we first investigated the expression of laminin α chains, which bind to cell surface receptors such as integrins, in the postnatal murine brain. We found that laminin α1, α2, α4, and α5 chains were expressed around blood vessels and OPCs attached the laminin α chain-positive vessels. We then evaluated the effect of these laminins on OPCs activity using recombinant laminin E8s (LME8s) that are minimally active fragments of the laminin isoforms. OPCs attached on LM211E8, LM411E8, and LM511E8, containing laminin α2, α4, and α5 chains, respectively, through integrin β1. Further, these three LME8s promoted migration of OPCs, and OPC survival was prolonged on either LM411E8 or LM511E8 via the activation of focal adhesion kinase. Together, our findings suggest that laminins expressed surrounding blood vessels positively regulate migration and survival of OPCs through the integrin β1-FAK pathway.
Highlights
Oligodendrocyte precursor cells (OPCs), alternatively called O2A cells, NG2 cells, or polydendrocytes, are one of glia cells in the central nervous system (CNS) and are differentiated into oligodendrocytes in the white matter for myelination, which accomplishes rapid salutatory conduction of nerve impulses and contribute to axonal integrity[1]
The expression of laminin α1, α2, α4, and α5 chains, but not α3 chain, was observed in basement membranes surrounding blood vessels, and Venus positive oligodendrocyte precursor cells (OPCs) contacted the vessels that expressed these laminin α chains (Fig. 1a,b). We confirmed these results by immunostaining with antibodies against laminin α chains and an OPC marker Olig[2] (Fig. 1c) and identified blood vessels using an antibody against an endothelial cell marker CD31 in the WT tissues (Fig. 1d)
We showed that the expression of laminin α1, α2, α4, and α5 chains was observed surrounding blood vessels at the early postnatal brain and OPCs attached to the vessels expressed these laminin isoforms
Summary
Oligodendrocyte precursor cells (OPCs), alternatively called O2A cells, NG2 cells, or polydendrocytes, are one of glia cells in the central nervous system (CNS) and are differentiated into oligodendrocytes in the white matter for myelination, which accomplishes rapid salutatory conduction of nerve impulses and contribute to axonal integrity[1]. OPCs arise from the ventricular/subventricular zone (VZ/SVZ) in the CNS tissues and migrate to the targeted areas for their differentiation[3]. Throughout this dynamic process, OPCs need to obtain survival signal from growth factors or cytokines and from cell adhesion on extracellular matrix proteins. A previous study revealed that the expression of laminin β1 and γ1 chains, which are components of major laminin isoforms, was analyzed in the brain tissue at the early postnatal stage, when oligodendrogenesis dynamically occurs, and OPC survival was reduced in laminin α2. LME8s containing laminin α2, α4, and α5 chains promoted OPC attachment and migration, and OPC survival was activated on α4 and α5 chains via focal adhesion kinase (FAK). This is the first study to evaluate all of the laminin α chains for OPC development and to reveal their activities
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
