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Publication : Rnd2 differentially regulates oligodendrocyte myelination at different developmental periods.

First Author  Miyamoto Y Year  2021
Journal  Mol Biol Cell Volume  32
Issue  8 Pages  769-787
PubMed ID  33596091 Mgi Jnum  J:309719
Mgi Id  MGI:6759605 Doi  10.1091/mbc.E20-05-0332
Citation  Miyamoto Y, et al. (2021) Rnd2 differentially regulates oligodendrocyte myelination at different developmental periods. Mol Biol Cell 32(8):769-787
abstractText  In the CNS, oligodendrocyte precursor cells differentiate into oligodendrocytes to wrap their plasma membranes around neuronal axons, generating mature neural networks with myelin sheaths according to spatial and temporal patterns. While myelination is known to be one of the most dynamic cell morphological changes, the overall intrinsic and extrinsic molecular cues controlling myelination remain to be fully clarified. Here, we describe the biphasic roles of Rnd2, an atypical branch of the Rho family GTPase, in oligodendrocyte myelination during development and after maturation in mice. Compared with littermate controls, oligodendrocyte-specific Rnd2 knockout mice exhibit decreased myelin thickness at the onset of myelination but increased myelin thickness in the later period. Larger proportions of Rho kinase and its substrate Mbs, the signaling unit that negatively regulates oligodendrocyte myelination, are phosphorylated at the onset of myelination, while their smaller proportions are phosphorylated in the later period. In addition, we confirm the biphasic role of Rnd2 through experiments with oligodendrocyte-specific Rnd2 transgenic mice. We conclude that Rnd2 positively regulates myelination in the early myelinating period and negatively regulates myelination in the later period. This unique modulator thus plays different roles depending on the myelination period.
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