Investigating Wnt signaling in the developing and adult mouse spinal cord
- Ependymal cells in the adult mammalian spinal cord are thought to be a population of "latent neural stem cells" with more regenerative potential than any other cell types in the adult spinal cord. In spite of their unique functions, the molecular signals that regulate ependymal cells in the postnatal and adult spinal cord remain poorly understood. In addition, there remain many gaps in our knowledge about the developmental origin and the generation of spinal cord ependymal cells. In Chapter 3, I begin my investigation of the developmental origin of spinal cord ependymal cells by analyzing Wnt-responsive neural progenitor cells in the developing spinal cord and show that Wnt signaling activity is concentrated in the dorsal midline neural progenitor cells throughout embryogenesis. Ependymal cells appear to be generated in a ventral to dorsal direction, with the dorsal midline ependymal cells generated last. Indeed, they are derived from Wnt-responsive dorsal midline radial glial cells give rise to towards the end of embryogenesis. These results suggest an important role of Wnt signaling in ependymal cell generation and highlights a region-specific allocation of ependymal cells which is consistent with the process during both neurogenesis and gliogenesis. In Chapters 4-6, I demonstrate that ependymal cells in the postnatal and adult spinal cord continue to be dependent on Wnt-signaling. Inhibiting Wnt signaling results in impaired ependymal cell proliferation. Ependymal cells also produce Wnt ligands which are required for maintaining ependymal cell proliferation. In Chapter 7, I investigate another Wnt-responsive cell population in the developing and adult spinal cord -- astrocytes. I also show evidence suggesting that Wnt signaling may be enriching for a more proliferative population of astrocytes at the periphery of the white matter, which serve as a source of new astrocytes in the adult spinal cord. Lastly in Chapter 8, I describe our efforts in elucidating the contribution of Wnt-responsive cells to long term glial scar formation after spinal cord injury. Taken together, these studies highlight the importance of Wnt signaling in the ependymal cell population throughout development, postnatal growth and homeostasis. The results also provide insights into the involvement of Wnt signaling in astrocyte proliferation and scar formation after spinal cord injury.
|Type of resource
|electronic; electronic resource; remote
|1 online resource.
|Stanford University, Department of Developmental Biology.
|Nusse, Roel, 1950-
|Nusse, Roel, 1950-
|Statement of responsibility
|Submitted to the Department of Developmental Biology.
|Thesis (Ph.D.)--Stanford University, 2017.
- © 2017 by Liujing Xing
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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