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TIP30 inhibits oligodendrocyte precursor cell differentiation via cytoplasmic sequestration of Olig1
Author(s) -
Yang Wenjing,
Xiao Lin,
Li Cui,
Liu Xiuyun,
Liu Mingdong,
Shao Qi,
Wang Dan,
Huang Aijun,
He Cheng
Publication year - 2015
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.22778
Subject(s) - remyelination , oligodendrocyte , gene knockdown , microbiology and biotechnology , biology , myelin , transcription factor , cellular differentiation , neuroscience , precursor cell , cell , central nervous system , cell culture , gene , genetics
Differentiation of oligodendrocyte precursor cells (OPCs) is a prerequisite for both developmental myelination and adult remyelination in the central nervous system. The molecular mechanisms underlying OPC differentiation remain largely unknown. Here, we show that the thirty‐kDa HIV‐1 Tat interacting protein (TIP30) is a negative regulator in oligodendrocyte development. The TIP30 −/− mice displayed an increased myelin protein level at postnatal day 14 and 21. By using a primary OPC culture system, we demonstrated that overexpression of TIP30 dramatically inhibited the stage progression of differentiating OPCs, while knockdown of TIP30 enhanced the differentiation of oligodendroglial cells remarkably. Moreover, overexpression of TIP30 was found to sequester the transcription factor Olig1 in the cytoplasm and weaken its nuclear translocation due to the interaction between TIP30 and Olig1, whereas knockdown of TIP30 led to more Olig1 localized in the nucleus in the initiation stage during OPC differentiation. In the cuprizone‐induced demyelination model, there was a dramatic increase in NG2‐expressing cells with nuclear location of Olig1 in the corpus callosum during remyelination. In contrast, within chronic demyelinated lesions in multiple sclerosis, TIP30 was abnormally expressed in NG2‐expressing cells, and few nuclear Olig1 was observed in these cells. Taken together, our findings suggest that TIP30 plays a negative regulatory role in oligodendroglial differentiation. GLIA 2015;63:684–698