Genetic Evidence that Dorsal Spinal Oligodendrocyte Progenitor Cells are Capable of Myelinating Ventral Axons Effectivel
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ORIGINAL ARTICLE
Genetic Evidence that Dorsal Spinal Oligodendrocyte Progenitor Cells are Capable of Myelinating Ventral Axons Effectively in Mice Minxi Fang1 • Qian Yu1,2 • Baiyan Ou1 • Hao Huang1 • Min Yi1 • Binghua Xie1 Aifen Yang1 • Mengsheng Qiu1 • Xiaofeng Xu1
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Received: 15 January 2020 / Accepted: 30 June 2020 Shanghai Institutes for Biological Sciences, CAS 2020
Abstract In the developing spinal cord, the majority of oligodendrocyte progenitor cells (OPCs) are induced in the ventral neuroepithelium under the control of the Sonic Hedgehog (Shh) signaling pathway, whereas a small subset of OPCs are generated from the dorsal neuroepithelial cells independent of the Shh pathway. Although dorsallyderived OPCs (dOPCs) have been shown to participate in local axonal myelination in the dorsolateral regions during development, it is not known whether they are capable of migrating into the ventral region and myelinating ventral axons. In this study, we confirmed and extended the previous study on the developmental potential of dOPCs in the absence of ventrally-derived OPCs (vOPCs). In NestinSmo conditional knockout (cKO) mice, when ventral oligodendrogenesis was blocked, dOPCs were found to undergo rapid amplification, spread to ventral spinal tissue, and eventually differentiated into myelinating OLs in the ventral white matter with a temporal delay, providing genetic evidence that dOPCs are capable of myelinating ventral axons in the mouse spinal cord. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12264-020-00593-5) contains supplementary material, which is available to authorized users. & Mengsheng Qiu [email protected] & Xiaofeng Xu [email protected] 1
Institute of Life Sciences, Zhejiang Key Laboratory of Organ Development and Regeneration, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou 310029, China
2
CAS Center for Excellence in Brain Science and Intelligence Technology, Institute of Neuroscience, Chinese Academy of Sciences, Shanghai 200031, China
Keywords Dorsally-derived OPCs OPC proliferation Oligodendrocyte differentiation Myelination
Introduction Oligodendrocytes (OLs) myelinate axons in the central nervous system (CNS) of vertebrates, enabling the rapid transmission of action potentials and providing structural and metabolic support to neurons. The specification and differentiation of oligodendrocyte progenitor cells (OPCs) are controlled by a complex network of extracellular signals, transcriptional factors, and epigenetic regulators [1]. Elucidation of the signaling pathways that control OL differentiation and myelin formation is a crucial prerequisite for developing novel strategies for myelin repair in several neurological diseases [2]. During embryonic development, OPCs are generated from distinct neural epithelial cells in the spinal cord and brain. The diversity of OPCs based on their origins is known as developmental heterogeneity [3]. In the developing mo
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