During development of the chick nervous system, a combination of Notch signalling and SoxB1 transcription factors (Sox1, Sox2 and Sox3) maintains a pool of self-renewing stem and progenitor cells. On p. 1843, Jonas Muhr and colleagues investigate whether Notch and SoxB1 proteins suppress neuronal differentiation through the same, or different, pathways. By expressing dominant-negative components of these pathways in chick embryos, they show that, although Notch requires SoxB1 to maintain progenitor characteristics,SoxB1 activity blocks neurogenesis independently of Notch. Notch represses the activity of bHLH proneural proteins via the bHLH transcription factors Hes1 and Hes5, but, the researchers found, also represses E-proteins - the heterodimerizing partners of proneural proteins - through a Hes-independent mechanism. SoxB1 proteins, by contrast, seem to maintain progenitors by creating a molecular environment in which E-proteins and proneural proteins cannot promote neuronal differentiation. As Notch, Sox and bHLH proteins are also expressed in muscle and neural crest progenitor populations, the authors suggest their results could be of broader relevance.