Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.27.316133v1?rss=1 Authors: Yellajoshyula, D., Pappas, S. S., Rogers, A., Choudhury, B., Cookson, M., Reed, X., Shakkottai, V., Giger, R., Dauer, W. T. Abstract: Mechanisms controlling myelination during CNS maturation play a pivotal role in the development and refinement of CNS circuits. The transcription factor THAP1 is essential for timing the inception of myelination during CNS maturation through a cell-autonomous role in the oligodendrocyte lineage. Here, we demonstrate that THAP1 modulates ECM composition by regulating glycosaminoglycan (GAG) catabolism within oligodendrocyte progenitor cells (OPCs). Thap1-/- OPCs accumulate and secrete excess GAGs, inhibiting their maturation through an auto-inhibitory mechanism. THAP1 controls GAG metabolism by binding to and regulating the GusB gene encoding {beta}-glucuronidase, a GAG-catabolic lysosomal enzyme. Applying GAG-degrading enzymes or overexpressing {beta}-glucuronidase rescues Thap1-/- OL maturation deficits in vitro and in vivo. Our studies establish lysosomal GAG catabolism within OPCs as a critical mechanism regulating oligodendrocyte development. Copy rights belong to original authors. Visit the link for more info