Eating up time: transcriptional regulation of temporal patterning

During neurogenesis, temporal patterning ensures that asymmetrically dividing neural stem cells (NSCs) generate different cell types in defined temporal windows, thus contributing to neuronal diversity. In Drosophila NSCs, temporal patterning is controlled by the sequential expression of the transcription factors Hunchback (Hb), Kruppel (Kr), Pdm and Castor (Cas). In this study, Andrea Brand and colleagues identify a novel Drosophila temporal transcription factor, Chronophage (Cph, or ‘time-eater’), that promotes the transition from the Pdm to Cas temporal windows. Cph, which is homologous to the mammalian transcription factors CTIP1 (Bcl11a) and CTIP2 (Bcl11b), achieves this by binding upstream of the castor gene to promote its expression. This is in contrast to other temporal factors, which usually act to repress the preceding factor. Interestingly, in cph mutant flies, as well as a reduction in Cas-specified neurons, Hb- and Kr-specified neurons are also expanded. Thus, Cph represses the competence of NSCs to generate early born neurons during the Hb and Kr temporal windows, functioning in two ways to drive this temporal switch and promote the generation of Cas-specified neurons. Thus, these findings enhance our understanding of the transcriptional events during neurogenesis and highlight Cph as a novel regulator of temporal patterning.