TY - JOUR
T1 - Class 3 semaphorins influence oligodendrocyte precursor recruitment and remyelination in adult central nervous system
AU - Piaton, Gabriele
AU - Aigrot, Marie-Stephane
AU - Williams, Anna
AU - Moyon, Sarah
AU - Tepavcevic, Vanja
AU - Moutkine, Imane
AU - Gras, Julien
AU - Matho, Katherine S.
AU - Schmitt, Alain
AU - Soellner, Heidi
AU - Huber, Andrea B.
AU - Ravassard, Philippe
AU - Lubetzki, Catherine
PY - 2011/4
Y1 - 2011/4
N2 - Oligodendrocyte precursor cells, which persist in the adult central nervous system, are the main source of central nervous system remyelinating cells. In multiple sclerosis, some demyelinated plaques exhibit an oligodendroglial depopulation, raising the hypothesis of impaired oligodendrocyte precursor cell recruitment. Developmental studies identified semaphorins 3A and 3F as repulsive and attractive guidance cues for oligodendrocyte precursor cells, respectively. We previously reported their increased expression in experimental demyelination and in multiple sclerosis. Here, we show that adult oligodendrocyte precursor cells, like their embryonic counterparts, express class 3 semaphorin receptors, neuropilins and plexins and that neuropilin expression increases after demyelination. Using gain and loss of function experiments in an adult murine demyelination model, we demonstrate that semaphorin 3A impairs oligodendrocyte precursor cell recruitment to the demyelinated area. In contrast, semaphorin 3F overexpression accelerates not only oligodendrocyte precursor cell recruitment, but also remyelination rate. These data open new avenues to understand remyelination failure and promote repair in multiple sclerosis.
AB - Oligodendrocyte precursor cells, which persist in the adult central nervous system, are the main source of central nervous system remyelinating cells. In multiple sclerosis, some demyelinated plaques exhibit an oligodendroglial depopulation, raising the hypothesis of impaired oligodendrocyte precursor cell recruitment. Developmental studies identified semaphorins 3A and 3F as repulsive and attractive guidance cues for oligodendrocyte precursor cells, respectively. We previously reported their increased expression in experimental demyelination and in multiple sclerosis. Here, we show that adult oligodendrocyte precursor cells, like their embryonic counterparts, express class 3 semaphorin receptors, neuropilins and plexins and that neuropilin expression increases after demyelination. Using gain and loss of function experiments in an adult murine demyelination model, we demonstrate that semaphorin 3A impairs oligodendrocyte precursor cell recruitment to the demyelinated area. In contrast, semaphorin 3F overexpression accelerates not only oligodendrocyte precursor cell recruitment, but also remyelination rate. These data open new avenues to understand remyelination failure and promote repair in multiple sclerosis.
KW - semaphorin
KW - oligodendrocyte precursor cell
KW - recruitment
KW - remyelination
KW - gain and loss of function
U2 - 10.1093/brain/awr022
DO - 10.1093/brain/awr022
M3 - Article
SN - 0006-8950
VL - 134
SP - 1156
EP - 1167
JO - Brain
JF - Brain
IS - 4
ER -