seven-up Controls switching of transcription factors that specify temporal identities of Drosophila neuroblasts.

Drosophila neuronal stem cell neuroblasts (NB) constantly change character upon division, to produce a different type of progeny at the next division. Transcription factors Hunchback (HB), Krüppel (KR), Pdm (PDM), etc. are expressed sequentially in each NB and act as determinants of birth-order identity. How a NB switches its expression profile from one transcription factor to the next is poorly understood. We show that the HB-to-KR switch is directed by the nuclear receptor Seven-up (SVP). SVP expression is confined to a temporally restricted subsection within the NB's lineage. Loss of SVP function causes an increase in the number of HB-positive cells within several NB lineages, whereas misexpression of svp leads to the loss of these early-born neurons. Lineage analysis provides evidence that svp is required to switch off HB at the proper time. Thus, svp modifies the self-renewal stem cell program to allow chronological change of cell fates, thereby generating neuronal diversity.