Involvement of Sema4D in differentiation/maturation of myelinating oligodendrocytes

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Oligodendrocyte (OL) precursor cells (OPCs) that can proliferate and generate OLs, and surve as the primary source of remyelinating cells, are contained in the adult brain. In this study, we showed that Sema4D, found as an axon guidance regulator, plays a role as a negative regulator of OL development. Sema4D-deficiency increased in number of OLs, but not OPCs, suggesting that Sema4D enhances OL survival and promotes OL development. OLs as well as neurons are quite vulnerable to ischemic stress but shows powerful restorative ability after brain injury. Recent studies show that adult brain has the capability to self-repair in response to stroke, suggesting that proliferation and differentiation into myelinating OLs are important in regeneration and repair after brain injury. Sema4D-deficiency enhanced cell proliferation and the number of OLs in the peri-infarct area, suggesting that counteracting inhibitors of Sema4D are possible to improve brain repair in response to cerebral ischemia.