A Notch-dependent transcriptional mechanism controls expression of temporal patterning factors in Drosophila medulla

Temporal patterning is an important mechanism for generating a great diversity of neuron subtypes from a seemingly homogenous progenitor pool in both vertebrates and invertebrates. Drosophila neuroblasts have been shown to be temporally patterned by sequentially expressed Temporal Transcription Factors (TTFs). These TTFs are proposed to form a transcriptional cascade based on mutant phenotypes, although direct transcriptional regulation between TTFs has not been verified in most cases. Furthermore, it is not known how the temporal transitions are coupled with generation of the appropriate number of neurons at each stage. We use neuroblasts of the Drosophila optic lobe medulla to address these questions, and show that the expression of TTFs Sloppy-paired 1/ 2 (Slp1/2) is regulated at transcriptional level directly by two other TTFs and the cell-cycle dependent Notch signaling through two cis-regulatory elements. We also show that supplying transcriptional active Notch can rescue the delayed transition into the Slp stage in cell cycle arrested neuroblasts. Our findings reveal how an interplay between temporal patterning, the neuroblast cell cycle and key signaling pathways such as Notch achieves precise regulation of patterning transcription factor gene expression that is characteristic of these programs.