title: Somatodendritic Expression of JAM2 Inhibits Oligodendrocyte Myelination.
abstract: Myelination occurs selectively around neuronal axons to increase the efficiency and velocity of action potentials. While oligodendrocytes are capable of myelinating permissive structures in the absence of molecular cues, structurally permissive neuronal somata and dendrites remain unmyelinated. Utilizing a purified spinal cord neuron-oligodendrocyte myelinating co-culture system, we demonstrate that disruption of dynamic neuron-oligodendrocyte signaling by chemical cross-linking results in aberrant myelination of the somatodendritic compartment of neurons. We hypothesize that an inhibitory somatodendritic cue is necessary to prevent non-axonal myelination. Using next-generation sequencing and candidate profiling, we identify neuronal junction adhesion molecule 2 (JAM2) as an inhibitory myelin-guidance molecule. Taken together, our results demonstrate that the somatodendritic compartment directly inhibits myelination and suggest a model in which broadly indiscriminate myelination is tailored by inhibitory signaling to meet local myelination requirements.
authors: Department of Neurology and Program in Neuroscience, University of California, San Francisco, San Francisco, CA 94143, USA.
authors: Stephanie A
authors: SA
authors: Redmond
authors: Department of Neurology and Program in Neuroscience, University of California, San Francisco, San Francisco, CA 94143, USA.
authors: Feng
authors: F
authors: Mei
authors: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors: Yael
authors: Y
authors: Eshed-Eisenbach
authors: Department of Neurology and Program in Neuroscience, University of California, San Francisco, San Francisco, CA 94143, USA.
authors: Lindsay A
authors: LA
authors: Osso
authors: Bioinformatics Unit, Life Sciences Core Facilities, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors: Dena
authors: D
authors: Leshkowitz
authors: Department of Neurology and Program in Neuroscience, University of California, San Francisco, San Francisco, CA 94143, USA.
authors: Yun-An A
authors: YA
authors: Shen
authors: Departments of Neurobiology and Ophthalmology, Duke University School of Medicine, Durham, NC 27703, USA.
authors: Jeremy N
authors: JN
authors: Kay
authors: Centre de Recherche en Cancérologie de Marseille, Inserm, CNRS, Aix-Marseille University, UMR1068, 13284 Marseille, France.
authors: Michel
authors: M
authors: Aurrand-Lions
authors: Centre for Neuroregeneration, Centre for Multiple Sclerosis Research, Euan MacDonald Centre for Motor Neurone Disease Research, University of Edinburgh, Edinburgh EH16 4SB, UK.
authors: David A
authors: DA
authors: Lyons
authors: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 7610001, Israel. Electronic address: peles@weizmann.ac.il.
authors: Elior
authors: E
authors: Peles
authors: Department of Neurology and Program in Neuroscience, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: jonah.chan@ucsf.edu.
authors: Jonah R
authors: JR
authors: Chan
mesh_terms: D000818:Animals; D018920:Coculture Techniques; D062765:Junctional Adhesion Molecule B / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000378:metabolism* / Q000648:ultrastructure; D009836:Oligodendroglia / Q000378:metabolism* / Q000648:ultrastructure; D061251:Primary Cell Culture; D051381:Rats; D013116:Spinal Cord / Q000502:physiology / Q000648:ultrastructure
chemical_list: D062765:Junctional Adhesion Molecule B