The sonic hedgehog pathway mediates central regulation of cerebellar development and sarcoma phenotypic outcome

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.