Novel origins of medulloblastoma from Olig2+ progenitors of the rhombic lip

Abstract

The most common malignant pediatric brain tumor, medulloblastoma (MB), arises from so far undefined progenitor cells within the cerebellum. Here, we identify a novel population of progenitor cells within the rhombic lip defined by expression of the transcription factor Olig2. Conditional activation of Sonic hedgehog signaling in these progenitors produces MB globally similar to those originating from unipotent Math1+ granule neuron precursors. All tumors exhibit multilineage differentiation and proliferating Olig2+ cells, similar to human medulloblastoma. These studies suggest that MB may originate from diverse populations of progenitor cells, in addition to those in the EGL, but have a convergent stem‐cell phenotype even when derived from non‐stem cell populations.