TY - JOUR
T1 - Neuregulin 1 type III improves peripheral nerve myelination in a mouse model of congenital hypomyelinating neuropathy
AU - Belin, Sophie
AU - Ornaghi, Francesca
AU - Shackleford, Ghjuvan'Ghjacumu
AU - Wang, Jie
AU - Scapin, Cristina
AU - Lopez-Anido, Camila
AU - Silvestri, Nicholas
AU - Robertson, Neil
AU - Williamson, Courtney
AU - Ishii, Akihiro
AU - Taveggia, Carla
AU - Svaren, John
AU - Bansal, Rashmi
AU - Schwab, Markus H.
AU - Nave, Klaus
AU - Fratta, Pietro
AU - D'Antonio, Maurizio
AU - Poitelon, Yannick
AU - Feltri, M. Laura
AU - Wrabetz, Lawrence
PY - 2019/4/15
Y1 - 2019/4/15
N2 - 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.
AB - 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.
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U2 - 10.1093/hmg/ddy420
DO - 10.1093/hmg/ddy420
M3 - Article
C2 - 30535360
AN - SCOPUS:85064208221
SN - 0964-6906
VL - 28
SP - 1260
EP - 1273
JO - Human Molecular Genetics
JF - Human Molecular Genetics
IS - 8
ER -