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Open AccessArticle

miR-7 Controls the Dopaminergic/Oligodendroglial Fate through Wnt/β-catenin Signaling Regulation

Genome Institute of Singapore, A-STAR, Singapore 138672, Singapore
Department of Biology, University of Padova, 35131 Padova, Italy
Institute of Molecular and Cell Biology, A-STAR, Singapore 138632, Singapore
Department of Biological Sciences, National University of Singapore, Singapore 117558, Singapore
Department of Pharmacology, National University of Singapore, Singapore 117559, Singapore
International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Cells 2020, 9(3), 711;
Received: 26 December 2019 / Revised: 7 March 2020 / Accepted: 11 March 2020 / Published: 13 March 2020
(This article belongs to the Special Issue Signaling Pathway Analysis and Disease Modeling in Zebrafish)
During the development of the central nervous system, the proliferation of neural progenitors and differentiation of neurons and glia are tightly regulated by different transcription factors and signaling cascades, such as the Wnt and Shh pathways. This process takes place in cooperation with several microRNAs, some of which evolutionarily conserved in vertebrates, from teleosts to mammals. We focused our attention on miR-7, as its role in the regulation of cell signaling during neural development is still unclear. Specifically, we used human stem cell cultures and whole zebrafish embryos to study, in vitro and in vivo, the role of miR-7 in the development of dopaminergic (DA) neurons, a cell type primarily affected in Parkinson’s disease. We demonstrated that the zebrafish homologue of miR-7 (miR-7a) is expressed in the forebrain during the development of DA neurons. Moreover, we identified 143 target genes downregulated by miR-7, including the neural fate markers TCF4 and TCF12, as well as the Wnt pathway effector TCF7L2. We then demonstrated that miR-7 negatively regulates the proliferation of DA-progenitors by inhibiting Wnt/β-catenin signaling in zebrafish embryos. In parallel, miR-7 positively regulates Shh signaling, thus controlling the balance between oligodendroglial and DA neuronal cell fates. In summary, this study identifies a new molecular cross-talk between Wnt and Shh signaling pathways during the development of DA-neurons. Being mediated by a microRNA, this mechanism represents a promising target in cell differentiation therapies for Parkinson’s disease. View Full-Text
Keywords: miR-7; zebrafish; Wnt; Shh; Tcf; dopaminergic neurons; oligodendrocytes; glia miR-7; zebrafish; Wnt; Shh; Tcf; dopaminergic neurons; oligodendrocytes; glia
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Adusumilli, L.; Facchinello, N.; Teh, C.; Busolin, G.; Le, M.T.; Yang, H.; Beffagna, G.; Campanaro, S.; Tam, W.L.; Argenton, F.; Lim, B.; Korzh, V.; Tiso, N. miR-7 Controls the Dopaminergic/Oligodendroglial Fate through Wnt/β-catenin Signaling Regulation. Cells 2020, 9, 711.

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