Identifying the cellular origins of medulloblastoma – the most common malignant brain tumor in children – may help focus treatment on cell types responsible for tumor initiation. Previous research has linked Sonic hedgehog signaling in neuronal cell precursors within the developing cerebellum to medulloblastoma.
Now, Chin Chiang, professor of cell and developmental biology, and colleagues demonstrate that “turning on” Sonic hedgehog signaling in a different cell type – hindbrain roof plate cells – leads to medulloblastoma. The roof plate cells are a specialized tissue that function as a signaling center regulating neural patterning. Previous studies had suggested that the hindbrain roof plate was restricted in its potential and contributed only to non-neural choroid plexus epithelial cells.
The new studies, reported in April in PLoS ONE, demonstrate that the hindbrain roof plate contributes not only to choroid plexus but also to multiple neuronal and glial cell types in the cerebellum. The findings also show that hindbrain roof plate cells are susceptible to tumorigenic transformation by deregulated Sonic hedgehog signaling.
This research was supported by grants from the National Institute of General Medical Sciences (GM007347), the National Cancer Institute (CA068485) and the National Institute of Neurological Disorders and Stroke (NS042205) of the National Institutes of Health and from the Children’s Brain Tumor Foundation.
