Necl-4/SynCAM-4 Is Expressed in Myelinating Oligodendrocytes but Not Required for Axonal Myelination

Ying Zhu,Hao Huang,Jiangang Yuan,Hong Li,Yin Bin,Boqin Qiang,Xiaofeng Zhao,Xiaozhong Peng,Jinsil Park,Mengsheng Qiu,Kehan Li,Xuemei Hu,Tai An

doi:10.1371/journal.pone.0064264

Abstract

The timing and progression of axonal myelination are precisely controlled by intercellular interactions between neurons and glia in development. Previous in vitro studies demonstrated that Nectin like 4 (Necl-4, also known as cell adhesion molecule Cadm-4 or SynCAM-4) plays an essential role in axonal myelination by Schwann cells in the peripheral nervous system (PNS). However, the role of Necl-4 protein in axonal myelination in the developing central nervous system (CNS) has remained unknown. In this study, we discovered upregulation of Necl-4 expression in mature oligodendrocytes at perinatal stages when axons undergo active myelination. We generated Necl4 gene knockout mice, but found that disruption of Necl-4 gene did not affect oligodendrocyte differentiation and myelin formation in the CNS. Surprisingly, disruption of Necl-4 had no significant effect on axonal myelination in the PNS either. Therefore, our results demonstrated that Necl-4 is dispensable for axonal myelination in the developing nervous system.

Highlights

In vertebrate nervous system, internodal axons are wrapped by compact myelin sheaths, the specialized cellular membranes elaborated by myelinating glial cells
Starting from E18.5, expression of Necl-4 was detected in the white matter (Figure 1B), and the number of Necl-4+ cells gradually increased with time and reached the maximum between P7 and P15 (Figure 1E–F), the peak time of oligodendrocyte myelination in mouse spinal cords [4]
Previous studies described that Necl-4 is expressed by peripheral nervous system (PNS) neurons and Schwann cells, and mediates axonal myelination by heterophilic binding to its axonal partner Necl-1 [6,7]

Summary

Introduction

Internodal axons are wrapped by compact myelin sheaths, the specialized cellular membranes elaborated by myelinating glial cells. In the central nervous system (CNS), myelin sheaths are formed by oligodendrocytes. The progression of axonal myelination involves multiple steps, including adherence of oligodendrocytes to axons, spiraling of oligodendrocyte process around axons and the formation of compact myelin sheath [4]. Each of these steps is precisely regulated by the reciprocal communication between glial cells and neurons [4,5]

Methods

Results

Conclusion