MCDB Seminar: Dystonia transcription factor THAP1 modulates myelination by regulating ECM degradation in lysosomes

The development and function of the nervous system is profoundly influenced by interactions of neurons with glial cells and the extracellular matrix (ECM). Mechanisms regulating the generation of myelinating glia in the CNS to facilitate myelination during development and adulthood play an essential role in circuit plasticity and motor function. Our studies identified that the transcription factor THAP1 has a critical role in regulating the maturation of the oligodendrocyte progenitor cells (OPCs) to mature myelinating oligodendrocytes (OLs). Loss-of function mutations in the THAP1 gene cause the neurodevelopmental disorder DYT6 or DYT-THAP1 dystonia, a movement disorder effecting CNS motor function. THAP1 mediates this effect by regulating the content of chondroitin sulfate (CS) GAGs, a class of long unbranched polysaccharides and coreconstituents of extracellular matrix (ECM), within the OL lineage. Our study brings attention to a new cellular pathway that controls a ECM homeostasis, and to OPCs as an important cell type in ECM regulation. Regulation of the ECM by OPCs serves an autoregulatory function in controlling OL maturation and myelination during CNS development.

Note: This is a Wednesday rather than the usual Friday time.
2:00 - 3:00pm with Q&A to follow
Hybrid
1010 BSB and Zoom
https://umich.zoom.us/j/97632305866

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