PTCH1 and medulloblastoma: Mutations such as Ptch1 loss-of-function or Smo gain-of-function lead to constitutively active Shh signaling, which results in CGNP over-proliferation and medulloblastoma.13 A mouse model of medulloblastoma with an activating SmoM2 mutant transgene closely resembles human Shh-type medulloblastomas.45 The high Gli1 levels that we observed in P4 cerebellum and in medulloblastoma samples indicate active Shh signaling during cerebellum development and in Shh-type medulloblastoma formation (Figure 6a).