| Literature DB >> 30535360 |
Sophie Belin1,2,3, Francesca Ornaghi1,2,4,5, Ghjuvan'Ghjacumu Shackleford1,6, Jie Wang2, Cristina Scapin4, Camila Lopez-Anido7, Nicholas Silvestri6, Neil Robertson2, Courtney Williamson1, Akihiro Ishii8, Carla Taveggia9, John Svaren7, Rashmi Bansal8, Markus H Schwab10,11, Klaus Nave10, Pietro Fratta12, Maurizio D'Antonio4, Yannick Poitelon3, M Laura Feltri1,2,6,4, Lawrence Wrabetz1,2,6,4.
Abstract
Myelin sheath thickness is precisely regulated and essential for rapid propagation of action potentials along myelinated axons. In the peripheral nervous system, extrinsic signals from the axonal protein neuregulin 1 (NRG1) type III regulate Schwann cell fate and myelination. Here we ask if modulating NRG1 type III levels in neurons would restore myelination in a model of congenital hypomyelinating neuropathy (CHN). Using a mouse model of CHN, we improved the myelination defects by early overexpression of NRG1 type III. Surprisingly, the improvement was independent from the upregulation of Egr2 or essential myelin genes. Rather, we observed the activation of MAPK/ERK and other myelin genes such as peripheral myelin protein 2 and oligodendrocyte myelin glycoprotein. We also confirmed that the permanent activation of MAPK/ERK in Schwann cells has detrimental effects on myelination. Our findings demonstrate that the modulation of axon-to-glial NRG1 type III signaling has beneficial effects and improves myelination defects during development in a model of CHN.Entities:
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Year: 2019 PMID： 30535360 PMCID： PMC6452193 DOI： 10.1093/hmg/ddy420
Source DB: PubMed Journal: Hum Mol Genet ISSN： 0964-6906 Impact factor: 6.150