A gene regulatory architecture that controls region‐independent dynamics of oligodendrocyte differentiation
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- Martina Cantone
- Laboratory of Systems Tumor Immunology, Hautklinik Universitätsklinikum Erlangen and Friedrich‐Alexander‐Universität Erlangen‐Nürnberg Erlangen Germany
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- Melanie Küspert
- Institut für Biochemie, Emil‐Fischer‐Zentrum Friedrich‐Alexander‐Universität Erlangen‐Nürnberg Germany
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- Simone Reiprich
- Institut für Biochemie, Emil‐Fischer‐Zentrum Friedrich‐Alexander‐Universität Erlangen‐Nürnberg Germany
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- Xin Lai
- Laboratory of Systems Tumor Immunology, Hautklinik Universitätsklinikum Erlangen and Friedrich‐Alexander‐Universität Erlangen‐Nürnberg Erlangen Germany
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- Martin Eberhardt
- Laboratory of Systems Tumor Immunology, Hautklinik Universitätsklinikum Erlangen and Friedrich‐Alexander‐Universität Erlangen‐Nürnberg Erlangen Germany
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- Peter Göttle
- Neuroregeneration, Department of Neurology, Medical Faculty Heinrich‐Heine University Düsseldorf Germany
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- Felix Beyer
- Neuroregeneration, Department of Neurology, Medical Faculty Heinrich‐Heine University Düsseldorf Germany
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- Kasum Azim
- Neuroregeneration, Department of Neurology, Medical Faculty Heinrich‐Heine University Düsseldorf Germany
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- Patrick Küry
- Neuroregeneration, Department of Neurology, Medical Faculty Heinrich‐Heine University Düsseldorf Germany
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- Michael Wegner
- Institut für Biochemie, Emil‐Fischer‐Zentrum Friedrich‐Alexander‐Universität Erlangen‐Nürnberg Germany
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- Julio Vera
- Laboratory of Systems Tumor Immunology, Hautklinik Universitätsklinikum Erlangen and Friedrich‐Alexander‐Universität Erlangen‐Nürnberg Erlangen Germany
説明
<jats:title>Abstract</jats:title><jats:p>Oligodendrocytes (OLs) facilitate information processing in the vertebrate central nervous system via axonal ensheathment. The structure and dynamics of the regulatory network that mediates oligodendrogenesis are poorly understood. We employed bioinformatics and meta‐analysis of high‐throughput datasets to reconstruct a regulatory network underpinning OL differentiation. From this network, we identified families of feedforward loops comprising the transcription factors (TFs) Olig2, Sox10, and Tcf7l2 and their targets. Among the targets, we found eight other TFs related to OL differentiation, suggesting a hierarchical architecture in which some TFs (Olig2, Sox10, and Tcf7l2) regulate via feedforward loops the expression of others (Sox2, Sox6, Sox11, Nkx2‐2, Nkx6‐2, Hes5, Myt1, and Myrf). Model simulations with a kinetic model reproduced the mechanisms of OL differentiation only when in the model, Sox10‐mediated repression of Tcf7l2 by miR‐338/miR‐155 was introduced, a prediction confirmed in genetic functional experiments. Additional model simulations suggested that OLs from dorsal regions emerge through BMP/Sox9 signaling.</jats:p>
収録刊行物
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- Glia
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Glia 67 (5), 825-843, 2019-02-07
Wiley