List of proteins tested for their role in OPC differentiation
| Protein | Biological function | Cellular location |
|---|---|---|
| Myelin-associated glycoprotein (MAG) | Member of the Ig superfamily binding sialic acid (Kelm et al., 1994; Crocker et al., 1998); one of several white matter inhibitors of neurite outgrowth in vitro and axonal regeneration in vivo (Filbin, 2003); inhibits microtubule assembly by a Rho-kinase-dependent mechanism (Mimura et al., 2006). Deletion of MAG induces a developmental delay in OPC differentiation and myelin formation (Pernet et al., 2008). | Membrane |
| Nogo-A | Myelin-associated neurite outgrowth inhibitor. Nogo-A plays a role both in the restriction of axonal regeneration after injury and in structural plasticity in the CNS of higher vertebrates (Prinjha et al., 2000; Fournier et al., 2001). Deletion of Nogo-A induces a developmental delay in OPC differentiation and myelin formation (Pernet et al., 2008). | Membrane |
| Oligodendrocyte myelin glycoprotein (OMgp) | A glycosyl phosphatidyl inositol-linked protein and minor component of both CNS and PNS myelin. OMgp expression is also found in cells extending processes to nodes of Ranvier that may prevent aberrant sprouting from the node (Huang et al., 2005). OMgp may also exert antiproliferative effects on OPCs and induce OPC differentiation (Vourc'h and Andres, 2004) | Membrane |
| Brevican | Highly abundant proteoglycan in normal brain (Yamaguchi, 2000).; contributes to the nonpermissive environment for axon regeneration (Quaglia et al., 2008). | Extracellular matrix |
| Membrane | ||
| Secreted | ||
| Netrin-1 | Major neuronal guidance cue (Serafini et al., 1994); can provide both attractive and repulsive cues to neurons, depending on the receptors present and cellular context. | Extracellular matrix |
| Early studies have indicated that netrin-1 acts as chemorepellent for optic nerve-derived OPCs (Sugimoto et al., 2001). Similarly, it has been shown that addition of netrin-1 to the medium is able to repel OPCs in transmigration assays as well as negatively regulate OPC process formation during a time interval ranging from 30 min to 16 h following exposure (Jarjour et al., 2003). However, the same group subsequently reported that netrin-1 does not affect the differentiation of immature or mature OPCs in vitro (observation period, 24 h). Moreover, data included in our paper demonstrate that netrin-1 is able to exert positive effects on process formation, branching, and myelin-like sheet formation (Rajasekharan et al., 2009). The temporal switch from netrin-1-mediated chemorepulsion and process inhibition to process elaboration occurring in OPCs was subsequently shown to be dependent on RhoA signaling (Rajasekharan et al., 2009). The present experiment assessed the OPC response following 48 h of exposure to netrin-1 substrates and mirrors the results reported following prolonged exposure to netrin-1 (≥24 h) (Rajasekharan et al. 2010; Rajasekharan et al., 2009). | Secreted | |
| Myelin oligodendrocyte glycoprotein (MOG) | Target antigen for the experimental autoimmune encephalitis (Lebar et al., 1986); present on the outermost lamellae of mature CNS myelin. Its late appearance during myelinogenesis suggests that it contributes to myelin maturation or maintenance (Amor et al., 1994; Genain et al., 1999). | Membrane |