Investigating Early Effects Following Glia Cell Ablation in Medulloblastoma

Presenter: Kelsey Wahl, Chemistry

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. In our lab, medulloblastoma is modeled in mice by inducing heterozygous mutations in both the sonic hedgehog signaling receptor patched (Ptc) and the tumor suppressor gene p53. These mutations lead to a brain tumor in the cerebellum through over-proliferation of GNPs. From previous research, it is shown that unipotent GNPs in a tumor can somehow give rise to glia cells. In order to determine the role of glia cells within the tumor, they were selectively ablated through thymidine kinase (TK)-mediated cell ablation with administration of Ganciclovir (GCV). Amazingly, the proper dosing regime of GCV leads to complete tumor regression. To further understand the ablation process, we studied early time points during GCV injections to observe cellular processes within the tumor.