Evidence That ITPR2-Mediated Intracellular Calcium Release in Oligodendrocytes Regulates the Development of Carbonic Anhydrase II + Type I/II Oligodendrocytes and the Sizes of Myelin Fibers

Ruyi Mei; Linyu Huang; Mengyuan Wu; Chunxia Jiang; Aifen Yang; Huaping Tao; Kang Zheng; Junlin Yang; Wanhua Shen; Xianjun Chen; Xiaofeng Zhao; Mengsheng Qiu

doi:10.3389/fncel.2021.751439

Evidence That ITPR2-Mediated Intracellular Calcium Release in Oligodendrocytes Regulates the Development of Carbonic Anhydrase II + Type I/II Oligodendrocytes and the Sizes of Myelin Fibers

Front Cell Neurosci. 2021 Sep 22:15:751439. doi: 10.3389/fncel.2021.751439. eCollection 2021.

Authors

Ruyi Mei^{1

2}, Linyu Huang², Mengyuan Wu², Chunxia Jiang^{1

2}, Aifen Yang², Huaping Tao², Kang Zheng², Junlin Yang², Wanhua Shen², Xianjun Chen³, Xiaofeng Zhao², Mengsheng Qiu^{1

2}

Affiliations

¹ College of Life Sciences, Zhejiang University, Hangzhou, China.
² Zhejiang Key Laboratory of Organ Development and Regeneration, College of Life and Environmental Sciences, Institute of Developmental and Regenerative Biology, Hangzhou Normal University, Hangzhou, China.
³ Department of Physiology, Research Center of Neuroscience, Chongqing Medical University, Chongqing, China.

Abstract

Myelination of neuronal axons in the central nervous system (CNS) by oligodendrocytes (OLs) enables rapid saltatory conductance and axonal integrity, which are crucial for normal brain functioning. Previous studies suggested that different subtypes of oligodendrocytes in the CNS form different types of myelin determined by the diameter of axons in the unit. However, the molecular mechanisms underlying the developmental association of different types of oligodendrocytes with different fiber sizes remain elusive. In the present study, we present the evidence that the intracellular Ca²⁺ release channel associated receptor (Itpr2) contributes to this developmental process. During early development, Itpr2 is selectively up-regulated in oligodendrocytes coinciding with the initiation of myelination. Functional analyses in both conventional and conditional Itpr2 mutant mice revealed that Itpr2 deficiency causes a developmental delay of OL differentiation, resulting in an increased percentage of CAII⁺ type I/II OLs which prefer to myelinate small-diameter axons in the CNS. The increased percentage of small caliber myelinated axons leads to an abnormal compound action potentials (CAP) in the optic nerves. Together, these findings revealed a previously unrecognized role for Itpr2-mediated calcium signaling in regulating the development of different types of oligodendrocytes.

Keywords: ITPR2; axon diameter; conduction velocity; myelination; oligodendrocyte.