The Transmembrane Semaphorin Sema4D/CD100, an Inhibitor of Axonal Growth, Is Expressed on Oligodendrocytes and Upregulated after CNS Lesion

Abstract

Semaphorins are a family of secreted and membrane-bound proteins, known to regulate axonal pathfinding. Sema4D, also called CD100, was first isolated in the immune system where it is involved in B and T cell activation. We found that in the mouse, Sema4D is expressed in cells throughout the CNS white matter, with a peak during the myelination period. Double-labeling experiments with different markers of oligodendrocyte lineage such as olig1, olig2, platelet-derived growth factor receptor alpha, and proteolipid protein showed that Sema4D was expressed selectively by oligodendrocytes and myelin. The presence of Sema4D in myelin was confirmed using Western blot. Sema4D expression in myelinating oligodendrocytes was further observed using neuron-oligodendrocyte cocultures. Moreover, using stripe assay, we found that Sema4D is strongly inhibitory for postnatal sensory and cerebellar granule cell axons. This prompted us to examine whether Sema4D expression is modified after CNS injury. At 8 d after spinal cord lesions, Sema4D expression was strongly upregulated in oligodendrocytes at the periphery of the lesion. Sema4D-positive cells were not colabeled with the astrocyte marker GFAP, with the microglial and macrophagic marker isolectin B4, or with NG2, a marker of oligodendrocyte precursors. This upregulation was transient because from 1 month after the lesion, Sema4D expression was back to its normal level. These results indicate that Sema4D is a novel inhibitory factor for axonal regeneration expressed in myelin.

MICAL flavoprotein monooxygenases: Expression during neural development and following spinal cord injuries in the rat

“…Several recent studies support a prominent role for semaphorins in oligodendroglia biology. Oligodendrocyte progenitors and oligodendrocytes express a broad spectrum of semaphorins, neuropilins, plexins, and CRMPs (Cohen et al, 2003;Goldberg et al, 2004;Moreau-Fauvarque et al, 2003;Ricard et al, 2000Ricard et al, , 2001Spassky et al, 2002). Furthermore, semaphorins belonging to different subclasses, including class 3, can induce process retraction in oligodendrocyte progenitors and oligodendrocytes and can also orient the migration of oligodendrocyte progenitors in vitro (Cohen et al, 2003;Giraudon et al, 2004;Goldberg et al, 2004;Ricard et al, 2000Ricard et al, , 2001.…”

Stripe assay to examine axonal guidance and cell migration

“…With respect to the latter, neural crest cells 22 and oligodendrocytes 23,24 , but also non-neuronal cells such as tumor cells, have been studied 25 .…”

Degradation of Chondroitin Sulfate Proteoglycans Induces Sprouting of Intact Purkinje Axons in the Cerebellum of the Adult Rat

“…This function is primarily mediated by two sets of molecules, which include several myelin-associated proteins [Nogo-A, MAG, Omgp (oligodendrocyte-myelin glycoprotein), Sema4D (semaphorin 4D)] (Filbin, 2003;Moreau-Fauvarque et al, 2003;Schwab, 2004) and glial scar components, such as chondroitin sulfate proteoglycans (CSPGs) (Fawcett and Asher, 1999;Silver and Miller, 2004). Indeed, although these molecules are primarily known for hampering axon regeneration after injury, they are widely expressed in the intact brain, in which they may exert a constitutive regulatory action on physiological neuritic growth and plasticity.…”