SOX2 is a critical transcription regulator of progenitor/stem cell functions.35 In glioma and medulloblastoma, Sox2 promotes tumor progression and recurrence.43,44 At embryonic (E) day 14.5 (E14.5), robust SOX2 expression was detected in NOTCH-driven CPP, and CPC from Lmx1a-Cre;Ptchflox/flox;NICD1 (Lcre;Ptchcko;NICD1) mice that exhibited constitutive SHH signaling after conditional knockout of Patched 1 (Figure 2A).17,33 In contrast, SOX2 was expressed in a small fraction of tumor cells in Rb1/Trp53-deficient CPC (Figure 2B). Here, TP53 is linked to central nervous system cancer.