All Publications

  • The Lysosomal Transcription Factor TFEB Represses Myelination Downstream of the Rag-Ragulator Complex. Developmental cell Meireles, A. M., Shen, K., Zoupi, L., Iyer, H., Bouchard, E. L., Williams, A., Talbot, W. S. 2018; 47 (3): 319

    Abstract

    Myelin allows for fast and efficient axonal conduction, but much remains to be determined about the mechanisms that regulate myelin formation. To investigate the genetic basis of myelination, we carried out a genetic screen using zebrafish. Here, we show that the lysosomal G protein RagA is essential for CNS myelination. In rraga-/- mutant oligodendrocytes, target genes of the lysosomal transcription factor Tfeb are upregulated, consistent with previous evidence that RagA represses Tfeb activity. Loss of Tfeb function is sufficient to restore myelination in RagA mutants, indicating that hyperactive Tfeb represses myelination. Conversely, tfeb-/- single mutants exhibit ectopic myelin, further indicating that Tfeb represses myelination during development. In a mouse model of de- and remyelination, TFEB expression is increased in oligodendrocytes, but the protein is localized to the cytoplasm, and hence inactive, especially during remyelination. These results define essential regulators of myelination and may advance approaches to therapeutic remyelination.

    View details for PubMedID 30399334

  • The Lysosomal Transcription Factor TFEB Represses Myelination Downstream of the Rag-Ragulator Complex DEVELOPMENTAL CELL Meireles, A. M., Shen, K., Zoupi, L., Lyer, H., Bouchard, E. L., Williams, A., Talbot, W. S. 2018; 47 (3): 319-+

    View details for DOI 10.1016/j.devcel.2018.10.003

    View details for Web of Science ID 000449415400008