In contrast, stable re-expression of P53, RB1 or P53 and RB1 in a highly responsive Osx p53Rb KO osteosarcoma cell line (D12M) significantly reduced Gli1 mRNA in response to SHH ligand treatment and primary cilia frequency, supporting a direct connection between P53, RB1 and Hh pathway responsiveness and suggests that either Trp53 or Rb1 inactivation is sufficient for increased response to Hh ligand in this context (Supplementary Fig. 3). The gene discussed is SHH; the disease is osteosarcoma.