| My thesis work focused on understanding how oligodendrocytes, the myelinating cell type of the central nervous system, develop from ventral spinal cord precursors, called pMN cells, using zebrafish as a model organism. I analyzed the lineages of pMN cells and tested the roles of Hedgehog and Notch signaling for the specification of pMN precursors. This work led me to three main conclusions. First, pMN precursors produce several types of interneurons in addition to motoneurons and oligodendrocytes. Second, Hedgehog signaling establishes temporally and spatially biased fates of pMN cells. Third, Notch signaling controls neuronal fate decisions of pMN precursors. Additionally, using a forward genetic approach, I identified a novel gene that is critical for CNS and PNS myelination. Taken together, these results provide significant new insights to oligodendrocyte development and myelination, which may extend our knowledge and treatment of oligodendrocyte-related diseases such as multiple sclerosis. |
