Interestingly, all the tumors derived from the SOX2 knockout animals are stained positively with SOX2, suggesting that SOX2 is essential for tumorigenesis of osteosarcoma.160 Transgenic expression of SOX2 in the external granule cells exhibits more proliferate potential, but gives rise to medulloblastoma when Shh signaling is being constitutively active.196,197 Consistently, SOX2 deficiency suppresses the Shh signaling-induced tumor formation, implying that SOX2 expression in granule cell precursors is required for Shh-induced medulloblastoma120 (Table 1). This evidence concerns the gene SHH and neoplasm.