A tumor suppressive role for HH signaling would account for the benign, differentiated phenotype of GNs and for the decrease in proliferation of NB cells on transduction with Gli1. This hypothesis may be tested in vivo, and the role of HH signaling in NC development and PNT pathogenesis may be further elucidated, through xenograft studies and animal primary PNTs models, using targeted activation of Smo to drive HH activity [42] and targeted activation of MYCN to induce PNTs [43]. The gene discussed is SMO; the disease is neuroblastoma.