A gene regulatory architecture that controls region-independent dynamics of oligodendrocyte differentiation

Cantone M, Küspert M, Reiprich S, Lai X, Eberhardt M, Göttle P, Beyer F, Azim K, Küry P, Wegner M, Vera J (2019)

Publication Type: Journal article, Original article

Publication year: 2019

Journal

Glia Wiley-Blackwell

DOI: 10.1002/glia.23569

Abstract

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.

Authors with CRIS profile

Martina Cantone Department of Dermatology Melanie Küspert Lehrstuhl für Biochemie und Pathobiochemie Simone Reiprich Lehrstuhl für Biochemie und Pathobiochemie Xin Lai Department of Dermatology Martin Eberhardt Professur für Bioinformatik Michael Wegner Lehrstuhl für Biochemie und Pathobiochemie Julio Vera González Professur für Tumorimmunologie (Schwerpunkt Systembiologie)

Involved external institutions

Heinrich-Heine-Universität Düsseldorf DE Germany (DE)

How to cite

APA:

Cantone, M., Küspert, M., Reiprich, S., Lai, X., Eberhardt, M., Göttle, P.,... Vera, J. (2019). A gene regulatory architecture that controls region-independent dynamics of oligodendrocyte differentiation. Glia. https://doi.org/10.1002/glia.23569

MLA:

Cantone, Martina, et al. "A gene regulatory architecture that controls region-independent dynamics of oligodendrocyte differentiation." Glia (2019).

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