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Tcf7l2 is Tightly Controlled During Myelin Formation

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Abstract

Recent, studies have shown that Tcf7l2, an important transcription factor in Wnt pathway, plays critical roles in oligodendrocyte development. In this article we report a study showing that Tcf7l2 is under tight regulation during myelin formation. We have found that during early development, Tcf7l2 mRNA appears much earlier than the protein, suggesting a regulation at the translational level. We induced demyelination in a mouse model by a dietary toxin, where remyelination followed after a few weeks, and found that Tcf7l2 protein was expressed specifically during the active remyelination phase. Similarly, in human patients with demyelination diseases, Tcf7l2 protein expression was specifically promoted in regions undergoing active remyelination. During remyelination, Tcf7l2 was only expressed in non-dividing oligodendrocyte precursors and was associated with modest levels of nuclear beta-catenin. We also documented that Tcf7l2 could form protein complex with Olig2, but not with Olig1. Our data showed that during myelin formation, Tcf7l2/beta-catenin is regulated temporally, spatially, and also at levels of expression. These data suggest a key role for Tcf7l2 in myelination/remyelination processes via a tightly controlled activation of Wnt/beta-catenin pathway and the interaction with Olig2.

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Acknowledgments

This research was supported by National Natural Science Foundation of China Grant NO 30860131 and NIH grant R01NS059893, NIH 2P20RR017702-061A1.

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Authors and Affiliations

  1. Department of Physiology, Basic Medical College of Nanchang University, Nanchang, 330006, Jiangxi, China

    Hui Fu

  2. Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 02115, USA

    Hui Fu

  3. Division of Neuro-Oncology, Department of Neurosciences, UC San Diego, Moores Cancer Center, La Jolla, CA, 92093, USA

    Santosh Kesari

  4. Department of Pediatrics, Kosair Children’s Hospital Research Institute, University of Louisville School of Medicine, Louisville, KY, 40202, USA

    Jun Cai

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  1. Hui Fu
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  2. Santosh Kesari
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  3. Jun Cai
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Corresponding author

Correspondence to Hui Fu.

Electronic supplementary material

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10571_2011_9778_MOESM1_ESM.tif

Supplementary Fig. 1. Double staining of Tcf7l2 (red) and beta-catenin (green) in P5 mouse ventrolateral spinal cord. Arrows point to the double-positive oligodendrocyte cells with low level of nuclear beta-catenin; arrowheads points to motoneurons expressing high level of nuclear beta-catenin

10571_2011_9778_MOESM2_ESM.tif

Supplementary Fig. 2. Tcf7l2 plays important roles in myelin formation. Tcf7l2 is regulated by transcription factors including Olig1/2, Nkx6.1, Nkx2.2, and Sox10. Tcf7l2 protein also interacts with other proteins, such as Olig2 and beta-Catenin, and such interaction might in turn control the expression of myelin genes (MBP, PLP,and CNPase). This summary is based on the data of this article and Fu et al. 2009

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Fu, H., Kesari, S. & Cai, J. Tcf7l2 is Tightly Controlled During Myelin Formation. Cell Mol Neurobiol 32, 345–352 (2012). https://doi.org/10.1007/s10571-011-9778-y

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