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Title page for ETD etd-12102013-063407

Type of Document Dissertation
Author Cheng, Frances Yun
Author's Email Address frances.y.cheng@vanderbilt.edu
URN etd-12102013-063407
Title Modulation of Sonic Hedgehog signaling alters cerebellar development and medulloblastoma formation
Degree PhD
Department Cell and Developmental Biology
Advisory Committee
Advisor Name Title
Chris Wright Committee Chair
Bruce Carter Committee Member
Ethan Lee Committee Member
Robert Coffey Committee Member
  • roof plate
  • medulloblastoma inhibition
  • Bergmann glia
Date of Defense 2013-09-16
Availability unrestricted
Cerebellar development is a complex process involving the tightly regulated proliferation, specification, migration, and connectivity of thousands of neurons and glia. Perturbations in signaling pathways important for these processes can have drastic consequences, including medulloblastoma formation. In this dissertation work I have focused on Sonic Hedgehog (Shh) signaling and its role in cerebellar development and formation of medulloblastoma. Our studies have identified a novel contribution of the multipotent hindbrain roof plate cell to diverse lineages in the cerebellum and its susceptibility to oncogenic transformation by deregulated Shh signaling, which leads to medulloblastoma formation. In addition, we have determined a previously unappreciated role for Shh signaling in specialized cerebellar glial cells, which functions to sustain proliferation of neighboring neuronal precursors. Last, we identify a small molecule as a novel and potent Hh pathway antagonist in multiple cell types, including Hh-responsive medulloblastoma cells. My work therefore offers insight into the diverse roles of Shh activity in the cerebellum during development and disease, which can provide insight into brain growth and the development of targeted therapies for disease processes.
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