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Title page for ETD etd-04162014-131844

Type of Document Dissertation
Author Fleming, Jonathan Tyler
Author's Email Address jonathan.t.fleming@vanderbilt.edu
URN etd-04162014-131844
Title The sonic hedgehog pathway mediates central regulation of cerebellar development and sarcoma phenotypic outcome
Degree PhD
Department Cell and Developmental Biology
Advisory Committee
Advisor Name Title
James R Goldenring, MD. PhD Committee Chair
Andrea Page-McCaw Committee Member
Anna Means, PhD Committee Member
David Miller, PhD Committee Member
  • Sonic hedgehog cerebellum sarcoma
Date of Defense 2014-01-22
Availability unrestricted
Sonic hedgehog (Shh) signaling regulates critical processes during embryonic development and

in homeostasis of adult tissues. Deregulated pathway activity is a major factor underlying the

etiology of numerous developmental disorders and cancers. In this dissertation, I investigated

early neonatal cerebellar development, where I identified that the Purkinje neuron utilizes bidirectional

distribution of Shh to centrally regulate neurogenesis, and to expand a previously

unappreciated stem cell – progenitor cell lineage in the white matter niche. Additionally, I

established a novel mouse model for a soft tissue sarcoma, Ewing’s sarcoma. These findings

provide new understanding of how the Purkinje neuron oversees cerebellar development, as well

as key insight into the molecular underpinnings of a Shh-driven sarcoma variant.

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