Sophie, B;
Ornaghi, F;
Shackleford, G;
Wang, J;
Scapin, C;
Lopez-Anido, C;
Silvestri, N;
... Wrabetz, L; + view all
(2018)
Neuregulin 1 type III reduces severity in a mouse model of Congenital Hypomyelinating Neuropathy.
bioRxiv: Cold Spring Harbor Laboratory.
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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 type III regulate Schwann cell fate and myelination. Here we ask if modulating neuregulin 1 type III levels in neurons would restore myelination in a model of congenital hypomyelinating neuropathy (CHN). Using a mouse model of CHN, we rescued the myelination defects by early overexpression of neuregulin 1 type III. Surprisingly, the rescue 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 (Pmp2) and oligodendrocyte myelin glycoprotein (Omg). 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 neuregulin 1 type III signaling has beneficial effects and restores myelination defects during development in a model of CHN.
| Type: | Working / discussion paper |
|---|---|
| Title: | Neuregulin 1 type III reduces severity in a mouse model of Congenital Hypomyelinating Neuropathy |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1101/386748 |
| Language: | English |
| Additional information: | The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
| Keywords: | Congenital Hypomyelinating Neuropathy, MAPK, myelin protein zero, neuregulin 1, Schwann cell |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10057855 |
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