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.
Ferri C, Quattrini A, D’Antonio M. Electron microscopy for the analysis of peripheral nerve myelin. Methods in Molecular Biology, in press.
Roberts SL, Dun XP, Doddrell RDS, Mindos T, Drake LK, Onaitis MW, Florio F, Quattrini A, Lloyd AC, D'Antonio M, Parkinson DB. Sox2 expression in Schwann cells inhibits myelination in vivo and induces influx of macrophages to the nerve. Development 2017 Sep 1;144(17):3114-3125.
Volpi VG, Touvier T, D'Antonio M. Endoplasmic reticulum protein quality control failure in myelin disorders. Front. Mol. Neurosci. 2017 Jan 4;9:162.
Riva N, Clarelli F, Domi T, Cerri F, Gallia F, Trimarco A, Brambilla P, Lunetta C, Lazzerini A, Lauria G, Taveggia C, Iannaccone S, Nobile-Orazio E, Comi G, D'Antonio M, Martinelli-Boneschi F, Quattrini A. Unraveling gene expression profiles in peripheral motor nerve from amyotrophic lateral sclerosis patients: insights into pathogenesis. Sci. Rep. 2016 Dec 16;6:39297.
Sidoli M, Musner N, Silvestri N, Ungaro D, D'Antonio M, Cavener DR, Feltri ML, Wrabetz L. Ablation of perk in schwann cells improves myelination in the S63del Charcot-Marie-Tooth 1B mouse. J. Neurosci. 2016 Nov 2;36(44):11350-11361.
Musner N, Sidoli M, Zambroni D, Del Carro U, Ungaro D, Ron D, D’Antonio M, Feltri ML and Wrabetz L. Perk ablation ameliorates myelination in a Charcot-Marie-Tooth 1B neuropathy mouse model. ASN Neuro 2016 Apr 19;8(2).
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 2015 Apr 10;348(6231):239-42.
D'Antonio M*, Musner N, Scapin C, Ungaro D, Del Carro U, Ron D, Feltri ML, Wrabetz L*. (*corresponding author). Resetting translational homeostasis restores myelination in CMT1B mice. J. Exp. Med. 2013 Apr 8; 210(4): 821–838.
D'Antonio M, Feltri ML and Wrabetz L. Myelin under stress. J. Neurosci. Res. 2009 Nov 15;87(15):3241-9.
D'Antonio M, Droggiti A, Feltri ML, Roes J, Wrabetz L, Mirsky R and Jessen KR. TGFb type II receptor signalling controls Schwann cell death and proliferation in developing nerves. J. Neurosci. 2006 Aug 16;26(33):8417-27.