The sonic hedgehog pathway mediates central regulation of cerebellar development and sarcoma phenotypic outcome
Fleming, Jonathan Tyler
:
2014-04-30
Abstract
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.