Nanog and Hedgehog (HH) are both essential regulators of stemness by promoting self-renewal in embryonic stem cells, during early embryonal development (Mitsui et al, 2003) and in cancer cells (Jeter et al, 2009). Two groups have now shown that HH signalling regulates Nanog expression in neural stem cells in the adult brain and in brain tumours. In this issue of The EMBO Journal, Po et al(2010) and Zbinden et al(2010) demonstrate that downstream effectors in the HH pathway, Gli1 and Gli2 directly bind to the Nanog promoter and thus activate Nanog expression (Figure 1A). Po et al (2010) use the cerebellum as experimental paradigm (Figure 1C) and show that Nanog is highly expressed in stem cells derived from the postnatal cerebellum and in medulloblastoma, a malignant brain tumour arising from the cerebellum in children. This work is complemented by a study by Zbinden et al(2010), who use glial tumours and tumour spheres to demonstrate that the Gli–Nanog axis promotes stemness and growth in gliomas (Figure 1B).