TAPP1 Represses the Differentiation of Oligodendrocyte and its Deficiency Accelerates Myelin Regeneration after Demyelin
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LETTER TO THE EDITOR
TAPP1 Represses the Differentiation of Oligodendrocyte and its Deficiency Accelerates Myelin Regeneration after Demyelinating Injuries Ruyi Mei1,2 • Jiaying Fu1 • Chunxia Jiang1,2 • Junlin Yang1 • Kang Zheng1 Aifen Yang1 • Mengsheng Qiu1 • Xiaofeng Zhao1
•
Received: 20 March 2020 / Accepted: 12 August 2020 Ó Shanghai Institutes for Biological Sciences, CAS 2020
Dear Editor, Myelin, the lipid-rich insulation that supports the integrity of axons, enables rapid conduction of nerve impulses and information flow to distant brain areas [1]. Oligodendrocytes (OLs) are glial cells that myelinate axons with specialized lipid membrane extensions [2]. OL progenitor cells (OPCs) arise from neural stem cells [3], and undergo proliferation before terminal differentiation and eventual myelination. Impairment at any stage of OL development can affect myelin formation. Dysfunction of OLs and CNS myelin causes devastating neurological disorders represented by multiple sclerosis [4]. In addition, emerging evidence has revealed deficits in OLs and myelin in psychiatric disorders such as schizophrenia [5]. Delineating the mechanisms that underlie OL differentiation is crucial to understand myelin formation, and is a critical prerequisite for the development of novel strategies against myelin-associated disorders. In the past decades, accumulating evidence has demonstrated that both extracellular signals and/or intracellular factors play crucial roles in governing OL differentiation and myelination [6]. Of these, many (e.g. myelin regulatory factor) are initially expressed in white-matter OLs at the myelinogenic stage and their expression is required for CNS myelination [7]. Recently, we discovered a pleckstrin & Xiaofeng Zhao [email protected] 1
Institute of Developmental and Regenerative Biology, Zhejiang Key Laboratory of Organ Development and Regeneration, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou 310036, China
2
The College of Life Sciences, Zhejiang University, Hangzhou 310058, China
homology domain-containing adapter protein - TAPP1 that is selectively expressed in differentiating or premyelinating OLs. In vitro studies have revealed that it functions as a repressor of OL differentiation as it suppresses OPC differentiation in culture [8]. However, the in vivo role of TAPP1 in OL development and axonal myelination is currently unknown. In the present study, we aimed to characterize the function of TAPP1 in myelin development and regeneration using genetic approaches and a chemically-induced axonal demyelination model. To determine the role of TAPP1 in OL differentiation and myelin development, we crossed TRE2-TAPP1-FLAG transgenic mice with PLP-tTA knock-in mice [9]. In the resulting double-transgenic (DTG) mice, the TAPP1 fused in-frame with the FLAG sequence at its C-terminus was induced in the OLs that initially expressed Plp (Fig. 1A). As illustrated in the postnatal day 7 (P7) spinal cord, FLAG was observed in whi
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