Investigation of Supportive Cues in Early Stages of Pediatric Brain Cancer

Presenter: Kelsey Wahl

Medulloblastoma is the most common type of malignant brain tumor in children. During cerebellar development, granule neuron precursor cells (GNPs) proliferate along the external germinal layer in response to the sonic hedgehog signaling pathway. Mutations in the sonic hedgehog signaling receptor patched (Ptc) lead to tumors in the cerebellum through over-proliferation of GNPs. Over 50% of mice with the mutation develop foci of ectopic cells on the surface of the cerebellum between 3-6 weeks. Observations suggest that the ectopic cells may represent a pre-neoplastic stage of medulloblastoma. Although GNPs are unipotent progenitors that only give rise to granule neurons, lineage tracing studies in our lab have indicated that tumorigenic GNPs can also differentiate into glial cells. To further understand this fate switch and determine if it occurs prior to tumor formation, we looked for glia presence in Ptc pre-neoplastic lesions (PNLs). The appearance of glia cells in the earliest stages of tumor formation could provide insight into their potential supporting role in the tumor and in tumor cell transformation.