Cau, E., and Blader, P. (2009) Notch activity in the nervous system: to switch or not switch?. Neural Development. 4:36.
The Notch pathway is instrumental for cell fate diversification during development. Pioneer studies conducted in Drosophila and more recent work performed in vertebrates have shown that in the nervous system, Notch is reiteratively employed when cells choose between two alternative fates, a process referred to as a binary fate decision. While the early (neural versus epidermal) fate decisions mainly involve an inhibitory effect of Notch on the neural fate, late fate decisions (choice between different subtypes of neural cells) have been proposed to involve a binary switch activity whereby Notch would be instructive for one fate and inhibitory for the other. We re-examine this binary switch model in light of two recent findings made in the vertebrate nervous system. First, in the zebrafish epiphysis, Notch is required to resolve a mixed identity through the inhibition of one specific fate. Second, in the murine telencephalon, Notch regulates the competence of neural progenitors to respond to the JAK/STAT pathway, thereby allowing for the induction of an astrocyte fate. In neither case is Notch instructive for the alternative fate, but rather cooperates with another signalling pathway to coordinate binary fate choices. We also review current knowledge on the molecular cascades acting downstream of Notch in the context of neural subtype diversification, a crucial issue if one is to determine Notch function as an instructive, permissive or inhibitory signal in the various cellular contexts where it is implicated. Finally, we speculate as to how such a 'non-switch' activity could contribute to the expansion of neuronal subtype diversity.