Neuroblast entry into quiescence is regulated intrinsically by the combined action of spatial Hox proteins and temporal identity factors

Neural stem cell quiescence is an important feature in invertebrate and mammalian central nervous system development, yet little is known about the mechanisms regulating entry into quiescence, maintenance of cell fate during quiescence, and exit from quiescence. Drosophila neural stem cells (called neuroblasts) provide an excellent model system for investigating these issues. Drosophila neuroblasts enter quiescence at the end of embryogenesis and resume proliferation during larval stages; however, no single neuroblast lineage has been traced from embryo into larval stages. Here, we establish a model neuroblast lineage, NB3-3, which allows us to reproducibly observe lineage development from neuroblast formation in the embryo, through quiescence, to the resumption of proliferation in larval stages. Using this new model lineage, we show a continuous sequence of temporal changes in the neuroblast, defined by known and novel temporal identity factors, running from embryonic through larval stages, and that quiescence suspends but does not alter the order of neuroblast temporal gene expression. We further show that neuroblast entry into quiescence is regulated intrinsically by two independent controls: spatial control by the Hox proteins Antp and Abd-A, and temporal control by previously identified temporal transcription factors and the transcription co-factor Nab.