PT  - JOURNAL ARTICLE
AU  - Lin Pan
AU  - Amelia Trimarco
AU  - Alice J. Zhang
AU  - Ko Fujimori
AU  - Yoshihiro Urade
AU  - Lu O. Sun
AU  - Carla Taveggia
AU  - Ye Zhang
TI  - Oligodendrocyte-lineage cell exocytosis and L-type prostaglandin D synthase promote oligodendrocyte development and myelination
AID  - 10.1101/2022.02.14.480339
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.02.14.480339
4099  - http://biorxiv.org/content/early/2022/02/14/2022.02.14.480339.short
4100  - http://biorxiv.org/content/early/2022/02/14/2022.02.14.480339.full
AB  - In the developing central nervous system, oligodendrocyte precursor cells (OPCs) differentiate into oligodendrocytes, which form myelin around axons. Oligodendrocytes and myelin are essential for the function of the central nervous system, as evidenced by the severe neurological symptoms that arise in demyelinating diseases such as multiple sclerosis and leukodystrophy. Although many cell-intrinsic mechanisms that regulate oligodendrocyte development and myelination have been reported, it remains unclear whether interactions among oligodendrocyte-lineage cells (OPCs and oligodendrocytes) affect oligodendrocyte development and myelination. Here, we show that blocking vesicle-associated membrane protein (VAMP) 1/2/3-dependent exocytosis from oligodendrocyte-lineage cells impairs oligodendrocyte development, myelination, and motor behavior in mice. Adding oligodendrocyte-lineage cell-secreted molecules to secretion-deficient OPC cultures partially restores the morphological maturation of oligodendrocytes. Moreover, we identified L-type prostaglandin D synthase as an oligodendrocyte-lineage cell-secreted protein that promotes oligodendrocyte development and myelination in vivo. These findings reveal a novel autocrine/paracrine loop model for the regulation of oligodendrocyte and myelin development.Competing Interest StatementYZ consulted for Ono Pharmaceutical.