Directional growth of developing myelin mediated by Wnt gradient and required for proper axon functions

Abstract

Axon-wrapping myelin sheaths formed by oligodendrocytes are essential for proper functions of the central nervous system. Although much is known about oligodendrocyte development, how the myelin dynamically forms remains unclear. Here we show the preferentially unidirectional extension of developing myelin mediated by Wnt gradient and required for proper axon functions. Using larval zebrafish as an in vivo model, we found that developing myelin in the spinal cord preferentially extends to the anterior end, and this process is dependent on an anterior-to-posterior Wnt4b gradient. Taking advantage of the large size of Mauthner-cell axons, we further showed that disruption of this directional extension impairs the even length distribution of myelin sheaths and faithful transduction of action potentials along the axon, and reduces the reliability of escape behavior. Thus, our study reveals a novel process for precise regulation of myelination, providing a new insight into myelin structuring and functioning.