Our data point to the existence of two independent proliferation pathways in GCPs: a Shh-dependent pathway that is dominant for GCP proliferation and type 2 MB tumour formation, and an Otx2-dependent pathway that is critical for proliferation of Otx2-expressing GCP subpopulation, and that becomes mandatory for long-term maintenance of type 2 MB tumour growth. Here, GLI3 is linked to neoplasm.