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Stage‐specific regulation of oligodendrocyte development by Hedgehog signaling in the spinal cord
Author(s) -
Xu Xiaofeng,
Yu Qian,
Fang Minxi,
Yi Min,
Yang Aifen,
Xie Binghua,
Yang Junlin,
Zhang Zunyi,
Dai Zhongmin,
Qiu Mengsheng
Publication year - 2020
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.23729
Subject(s) - smoothened , biology , oligodendrocyte , olig2 , hedgehog signaling pathway , sonic hedgehog , hedgehog , cellular differentiation , progenitor cell , myelin , progenitor , microbiology and biotechnology , neuroscience , signal transduction , stem cell , central nervous system , genetics , gene
Elucidation of signaling pathways that control oligodendrocyte (OL) development is a prerequisite for developing novel strategies for myelin repair in neurological diseases. Despite the extensive work outlining the importance of Hedgehog (Hh) signaling in the commitment and generation of OL progenitor cells (OPCs), there are conflicting reports on the role of Hh signaling in regulating OL differentiation and maturation. In the present study, we systematically investigated OPC specification and differentiation in genetically modified mouse models of Smoothened ( Smo ), an essential component of the Hh signaling pathway in vertebrates. Through conditional gain‐of‐function strategy, we demonstrated that hyperactivation of Smo in neural progenitors induced transient ectopic OPC generation and precocious OL differentiation accompanied by the co‐induction of Olig2 and Nkx2.2. After the commitment of OL lineage, Smo activity is not required for OL differentiation, and sustained expression of Smo in OPCs stimulated cell proliferation but inhibited terminal differentiation. These findings have uncovered the stage‐specific regulation of OL development by Smo‐mediated Hh signaling, providing novel insights into the molecular regulation of OL differentiation and myelin repair.