Research - Myelin
The main focus of this EM Core Unit is myelin, a membranous multi-layered structure which builds the so-called white matter in the brain. Myelin is made by oligodendrocytes in the central nervous system (CNS) and by Schwann cells in the peripheral nervous system (PNS). The myelin sheath is a key feature of long axons because it speeds up conduction velocity as much as 100 times that of non-myelinated axons due to saltatory action potential propagation. Apart from this, the myelin sheath has protecting and supporting functions for the myelinated axons.
By using mouse genetics we investigate the biology and function of the myelinating glia cells in the CNS and PNS. We are focusing on the mechanisms of myelin biogenesis, maintenance, and turnover. By electron microscopy, one astonishing feature of myelin is the appearance as a solid and rather non-dynamic structure. Moreover, myelin proteins are known to turn over very slowly. To study mechanisms of myelin maintenance, we apply inducible knock-out strategies in the adult mouse and observe spatial and temporal changes in the myelin ultrastructure.
Due to the intimate relationship between the myelin sheath and the wrapped axon, also called the axo-glial unit, pathological changes in the myelinating glia cell affect axonal integrity. We study morphological changes induced by myelin mutants to better understand the functions of the intact myelin sheath as well as processes in demyelinating disease and ageing. Impairment of the myelin sheath and its consequences are studied in demyelinating disease models of multiple sclerosis and neuromyelitis optica (Weil et al., 2016 and 2017).
Apart from mouse models we are also interested in evolutionary aspects of myelin development. To address questions in myelin evolution we selected an agnathan model species, the marine lamprey Petromyzon marinus, which does not possess myelin and represents a putative ancestral stage in vertebrate evolution before the emergence of myelin. To test the hypothesis that evolutionary progenitors of myelinating cells are conserved in this recent species we assessed the axo-glial units in the lateral line nerve (representing the PNS) and the spinal cord in the larval and adult stage of the marine lamprey with transmission EM and volume imaging by FIB-SEM as well as fluorescent in-situ hybridization (Weil et al, 2018).
Weil M-T, Möbius W, Winkler A, Ruhwedel T, Wrzos C, Romanelli E, Bennett JL, Enz L, Goebels N, Nave KA, Kerschensteiner M, Schaeren-Wiemers N, Stadelmann C, Simons M (2016) Loss of Myelin Basic Protein Function Triggers Myelin Breakdown in Models of Demyelinating Diseases. Cell Rep. Jul 12;16(2): 314-22.
Weil, M-T, Ruhwedel, T, Möbius W, and Simons, M. (2017) Intracerebral injections and ultrastructural analysis of high-pressure frozen brain tissue. Curr. Protoc. Neurosci. 78:2.27.1-2.27.18. doi: 10.1002/cpns.22
Weil M-T, Heibeck S, Töpperwien M, tom Dieck S, Ruhwedel T, Salditt T, Rodicio MC, Morgan JR, Nave K-A, Möbius W and Werner HB. (2018) Axonal Ensheathment in the Nervous System of Lamprey: Implications for the Evolution of Myelinating Glia. Journal of Neuroscience 18 July 2018, 38 (29) 6586-6596