Accelerated repair of demyelinated CNS lesions in the absence of non-muscle myosin IIB.
The oligodendrocyte (OL), the myelinating cell of the central nervous system, undergoes dramatic changes in the organization of its cytoskeleton as it differentiates from a precursor (oligodendrocyte precursor cells) to a myelin-forming cell. These changes include an increase in its branching cell processes, a phenomenon necessary for OL to myelinate multiple axon segments. We have previously shown that levels and activity of non-muscle myosin II (NMII), a regulator of cytoskeletal contractility, decrease as a function of differentiation and that inhibition of NMII increases branching and myelination of OL in coculture with neurons. We have also found that mixed glial cell cultures derived from NMIIB knockout mice display an increase in mature myelin basic protein-expressing OL compared with wild-type cultures. We have now extended our studies to investigate the role of NMIIB ablation on myelin repair following focal demyelination by lysolecithin. To this end, we generated an oligodendrocyte-specific inducible knockout model using a Plp-driven promoter in combination with a temporally activated CRE-ER fusion protein. Our data indicate that conditional ablation of NMII in adult mouse brain, expedites lesion resolution and remyelination by Plp+ oligodendrocyte-lineage cells when compared with that observed in control brains. Taken together, these data validate the function of NMII as that of a negative regulator of OL myelination in vivo and provide a novel target for promoting myelin repair in conditions such as multiple sclerosis.
Department of Biological Sciences, Hunter College, New York, New York; The Graduate Center, Molecular Cellular and Developmental Biology, The City University of New York, New York.
Tomasz
T
Rusielewicz
Jennifer
J
Nam
Evangelos
E
Damanakis
Gareth R
GR
John
Cedric S
CS
Raine
Carmen V
CV
Melendez-Vasquez
D000818:Animals; D000941:Antigens / Q000378:metabolism; D000071183:Autophagy-Related Proteins; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D003337:Corpus Callosum / Q000473:pathology; D020278:Demyelinating Autoimmune Diseases, CNS / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics; D008244:Lysophosphatidylcholines; D051379:Mice; D008822:Mice, Transgenic; D004676:Myelin Basic Protein / Q000378:metabolism; D018991:Myelin Proteolipid Protein / Q000235:genetics / Q000378:metabolism; D009186:Myelin Sheath / Q000473:pathology; D009416:Nerve Regeneration / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D024501:Nonmuscle Myosin Type IIB / Q000172:deficiency* / Q000235:genetics; D000076104:Oligodendrocyte Transcription Factor 2; D009836:Oligodendroglia / Q000473:pathology; D011509:Proteoglycans / Q000378:metabolism; D000099216:Chondroitin Sulfate Proteoglycan 4
D000941:Antigens; D000071183:Autophagy-Related Proteins; D051792:Basic Helix-Loop-Helix Proteins; D005904:Glial Fibrillary Acidic Protein; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins; D008244:Lysophosphatidylcholines; D004676:Myelin Basic Protein; D018991:Myelin Proteolipid Protein; D009419:Nerve Tissue Proteins; D024501:Nonmuscle Myosin Type IIB; D000076104:Oligodendrocyte Transcription Factor 2; D011509:Proteoglycans; D000099216:Chondroitin Sulfate Proteoglycan 4; C512773:Olig2 protein, mouse; C047516:Plp1 protein, mouse; C428743:Rb1cc1 protein, mouse
cytoskeleton; myosin II; oligodendrocytes; remyelination