Role of transmembrane semaphorin Sema6A in oligodendrocyte differentiation and myelination.
Myelination is regulated by extracellular proteins, which control interactions between oligodendrocytes and axons. Semaphorins are repulsive axon guidance molecules, which control the migration of oligodendrocyte precursors during normal development and possibly in demyelinating diseases. We show here that the transmembrane semaphorin 6A (Sema6A) is highly expressed by myelinating oligodendrocytes in the postnatal mouse brain. In adult mice, Sema6A expression is upregulated in demyelinating lesions in cuprizone-treated mice. The analysis of the optic nerve and anterior commissure of Sema6A-deficient mice revealed a marked delay of oligodendrocyte differentiation. Accordingly, the development of the nodes of Ranvier is also transiently delayed. We also observed an arrest in the in vitro differentiation of purified oligodendrocytes lacking Sema6A, with a reduction of the expression level of Myelin Basic Protein. Their morphology is also abnormal, with less complex and ramified processes than wild-type oligodendrocytes. In myelinating co-cultures of dorsal root ganglion neurons and purified oligodendrocytes we found that myelination is perturbed in absence of Sema6A. These results suggest that Sema6A might have a role in myelination by controlling oligodendrocyte differentiation.
CNRS, UMR 7102, Paris, France.
Frédéric
F
Bernard
Caroline
C
Moreau-Fauvarque
Céline
C
Heitz-Marchaland
Yvrick
Y
Zagar
Laura
L
Dumas
Stéphane
S
Fouquet
Xinhua
X
Lee
Zhaohui
Z
Shao
Sha
S
Mi
Alain
A
Chédotal
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D000943:Antigens, Differentiation / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D001921:Brain / Q000166:cytology; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D003471:Cuprizone / Q000633:toxicity; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology; D004195:Disease Models, Animal; D004622:Embryo, Mammalian; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008996:Monoamine Oxidase Inhibitors / Q000633:toxicity; D009154:Mutation / Q000502:physiology; D004676:Myelin Basic Protein / Q000378:metabolism; D018991:Myelin Proteolipid Protein / Q000235:genetics / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000378:metabolism; D009474:Neurons / Q000502:physiology; D000076104:Oligodendrocyte Transcription Factor 2; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D011901:Ranvier's Nodes / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000172:deficiency; D039961:Semaphorins / Q000172:deficiency / Q000378:metabolism*; D013234:Stem Cells / Q000502:physiology; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism
D000943:Antigens, Differentiation; D051792:Basic Helix-Loop-Helix Proteins; D001973:Bromodeoxyuridine; D003471:Cuprizone; D008996:Monoamine Oxidase Inhibitors; D004676:Myelin Basic Protein; D018991:Myelin Proteolipid Protein; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D039961:Semaphorins; D014157:Transcription Factors; C499047:Mbp protein, mouse; C403042:Mga protein, mouse; C522729:Olig2 protein, rat; C047516:Plp1 protein, mouse; C492113:Plxna2 protein, mouse; C492110:Plxna4 protein, mouse; C504203:Sema6a protein, mouse; C036505:oligodendrocyte O antigen, mouse