Big Question: Emergence of Structure in the Central Nervous System: A Challenge to the Current Model of Axon Myelin Sheath Assembly

Principal Investigators: Sara Szuchet, Neurology; Gregory A. Voth, Chemistry; Ka Yee Lee, Chemistry

Funding Type: Vision

Focus Area: Cognition

Big Idea: The critically important myelin sheath is a complex multi-membrane structure synthesized in the central nervous system by oligodendrocytes (OLGs). The sheath envelops axons and is a facilitator of rapid nerve conduction, also implicated in diseases such as multiple sclerosis. The prevailing hypothesis is that OLGs extend a process that upon circumnavigating the axon multiple times generates the multilayer myelin structure – a notion that has persisted for over 50 years. Using long-term OLG cultures we have recently observed the presence of “dark structures” accumulating in their cytoplasm. We found them to consist of tubules, and that there is an emergent transition of these tubular structures into a multilamellar organization not unlike the myelin sheath. We therefore challenge the prevailing concept of myelin sheath formation by advancing three bold new hypotheses: 1) myelin membranes (MyMs) exist as independent entities; 2) they are packaged and transported in special organelles; 3) the myelin sheath is generated by the fusion of MyMs. Confirmation of these hypotheses would represent a major landmark for neuroscience – in health and disease – and in cell biology and biophysics.