Sonic hedgehog signaling in brain development and diseases

Abstract

Sonic hedgehog (Shh) signaling regulates important biological processes during embryogenesis and adult homeostasis. Deregulation of this essential signaling pathway can lead to congenital defects and tumorigenesis. In this dissertation I explored the functional role of the cholesterol modification on Shh protein during central nervous system (CNS) patterning, determined previously unappreciated regulation of Shh pathway on hindbrain choroid plexus and cerebellum development, and established a novel mouse model for cerebellar tumor, medulloblastoma. These findings provide us new knowledge of how Shh signaling regulates various CNS organ development, as well as novel insights into the oncogenic processes in Shh-dependent brain tumor.