AUTHOR=Wang Wanchen , Shiraishi Ryo , Kawauchi Daisuke 

TITLE=Sonic Hedgehog Signaling in Cerebellar Development and Cancer

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=Volume 10 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.864035

DOI=10.3389/fcell.2022.864035

ISSN=2296-634X

ABSTRACT=The sonic hedgehog (SHH) pathway regulates the development of the central nervous system in vertebrates. Aberrant regulation of SHH signalling pathways often causes neurodevelopmental diseases and brain tumours. In the cerebellum, SHH secreted by Purkinje cells is a potent mitogen for granule cell progenitors, which are the most abundant cell type in the mature brain. While a reduction in SHH signalling induces cerebellar structural abnormalities, such as hypoplasia in various genetic disorders, constitutive activation of SHH signalling often induces medulloblastoma (MB), one of the most common pediatric malignant brain tumours. Based on the existing literature on canonical and non-canonical SHH signalling pathways, emerging basic and clinical studies are exploring novel therapeutic approaches for MBs by targeting SHH signalling at distinct molecular levels. In this review, we discuss the current consensus on SHH signalling mechanisms, their roles in cerebellar development and tumourigenesis, and the recent advances in clinical trials for MBs.