Genetics and cell biology
Biology of myelin
Myelin is a specialized structure that surrounds large axons and permits rapid conduction of signals. It is formed by oligodendrocytes in the central nervous system and Schwann cells in the peripheral nervous system. During development, these cells migrate with the axons that they will myelinate, and depend on those same axons for appropriate signals to survive and differentiate. Myelin-forming glia coordinately express a unique set of genes encoding myelin structural proteins, and enzymes that synthesize myelin lipids-this coordination is in large part transcriptionally-mediated. Mutations in these proteins, including myelin specific proteins such as P0 and PMP22, are associated in humans to hereditary neuropathies, collectively known as Charcot-Marie-Tooth (CMT) disease.
This unit is devoted to study the molecular mechanisms underlying these diseases, with the goal of developing effective therapeutic strategies.
Scapin C., Ferri C., Pettinato E., Bianchi F., Del Carro U., Feltri M.L., Kaufman R.J., Wrabetz L., D’Antonio M. Phosphorylation of eIF2alpha promotes Schwann cell differentiation and myelination in CMT1B mice with activated UPR, J. Neurosci. 40(42):8174-8187, 2020.
Volpi V.G., Ferri C., Fregno I., Del Carro U., Bianchi F., Scapin C., Pettinato E., Solda T., Feltri M.L., Molinari M., Wrabetz L., D'Antonio M. Schwann cells Er-associated degradation contributes to myelin maintenance in adult nerves and limits demyelination in CMT1B mice, PLoS Genetics, 15(4):e1008069, 2019, doi:10.1371/journal.pgen.1008069
Scapin C., Ferri C., Pettinato E., Zambroni D., Bianchi F., Del Carro U., Caruso D., Mitro N., Belin S., Pellegatta M., Taveggia C., Schwab M., Nave K.A., Feltri M.L., Wrabetz L., D’Antonio M., Enhanced Neuregulin-1 type-III signaling ameliorates neurophysiology and hypomyelination in a Charcot-Marie-Tooth type 1B mouse model. Hum. Mol. Genetics, 28(6): 992-1006, 2019, doi: 10.1093/hmg/ddy411
Volpi V.G., Pagani I., Ghezzi S., Iannacone M., D’Antonio M.*, Vicenzi E.*, Zika virus replication in dorsal root ganglia explants causes myelin disruption in Schwann cells, Scientific Reports, 8(1):10166, 2018 *co-last authors doi: 10.1038/s41598-018-28257-5
Ferri C., Quattrini A., D’Antonio M. Electron microscopy for the analysis of peripheral nerve myelin, Methods Mol. Bio. 1791:3-13, 2018 doi: 10.1007/978-1-4939-7862-5_1
Bai Y., Wu X., Brennan K.M., Wang D.S., D'Antonio M., Moran J., Svaren J., Shy M.E. Myelin protein zero mutations and the unfolded protein response in Charcot-Marie-Tooth disease type 1B. Ann. Clin. Transl. Neurol. 5(4):445-455, 2018 doi: 10.1002/acn3.543
Florio C., Scapin C., Ferri C., Feltri M.L., Wrabetz L., D’Antonio M. Sustained expression of negative regulators of myelination protects Schwann cells from dysmyelination in a Charcot-Marie-Tooth type 1B mouse model, J. Neurosci. 38(18):4275-4287, 2018, doi: 10.1523/JNEUROSCI.0201-18.2018
Volpi V.G., Touvier T., D'Antonio M. Endoplasmic Reticulum Protein Quality Control Failure in Myelin Disorders. Front. Mol. Neurosci. 9:162, 2017
Sidoli M., Musner N., Silvestri N., Ungaro D., D'Antonio M., Cavener D.R., Feltri M.L., Wrabetz L. Ablation of Perk in Schwann Cells Improves Myelination in the S63del Charcot-Marie-Tooth 1B Mouse, J. Neurosci. 36(44):11350-11361, 2016
Brügger V., Engler S , Pereira J.A., Rüff S., Horn M., Welzl H., Münger E., Vaquie A., SidiropouloS P., Somandin C., Lühmann T.C., D’Antonio M., Yamaguchi T., Matthias P., Suter U., Jacob C. HDAC1/2-dependent P0 expression maintains paranodal and nodal integrity through interactions with Neurofascin in adult peripheral nerves, PLOS Biology, 13 (9), 2015
Das I., Krzyzosiak A., Schneider K., Wrabetz L., D’Antonio M., Barry N., Sigurdardottir A., Bertolotti A. Preventing proteostasis diseases by selective inhibition of a phosphatase regulatory subunit. Science, 348(6231):239-42, 2015
Cermenati G., Audano M., Giatti S., Carozzi V., Porretta-Serapiglia C., Ferri C., Pettinato E., D’Antonio M., De Fabiani E., Crestani M., Scurati M., Azcoitia I., Cavaletti G., Garcia-Segura L.M., Melcangi R.C., Caruso D. and Mitro N. Lack of Sterol Regulatory Element Binding Factor 1c imposes glial fatty acid utilization leading to peripheral neuropathy, Cell Metabolism, 21(4): 571-583, 2015
D'Antonio M.*, Musner N., Scapin C., Ungaro D., Del Carro U., Ron D., Feltri M.L., Wrabetz L.* Resetting translational homeostasis restores myelination in CMT1B mice. J. Exp. Med. 210(4):821-38, 2013 *corresponding author
