Neural precursors often generate distinct cell types in a specific order, but the intrinsic or extrinsic cues regulating the timing of cell fate specification are poorly understood. Here we show that Drosophila neural precursors (neuroblasts) sequentially express the transcription factors Hunchback --> Krüppel --> Pdm --> Castor, with differentiated progeny maintaining the transcription factor profile present at their birth. Hunchback is necessary and sufficient for first-born cell fates, whereas Krüppel is necessary and sufficient for second-born cell fates; this is observed in multiple lineages and is independent of the cell type involved. We propose that Hunchback and Krüppel control early-born temporal identity in neuroblast cell lineages.

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The Drosophila embryonic central nervous system (CNS) develops from a bilateral neuroectoderm that forms adjacent to the specialized cells of the ventral midline. Neuroectoderm on each side of the ventral midline can be subdivided, on the basis of patterns of gene expression and neuroblast formation, into an orthogonal grid of four rows (1, 3, 5, 7) along the anteroposterior (AP) axis and three columns (ventral, intermediate, and dorsal) along the DV axis. The earliest neuroblast array has four neuroblasts in the ventral column, two in the intermediate column, and four in the dorsal column. Neuroblasts divide repeatedly to produce a series of smaller ganglion mother cells (GMCs), each of which produce two postmitotic neurons or glia. Every neuroblast is uniquely identifiable on the basis of its AP and DV position, and each generates a characteristic family of neurons and glia.Neuroblast formation is regulated by the proneural genes achaete, scute, and lethal of scute (for review, see Campos-Ortega 1993). Each of these proneural genes is expressed in clusters of 4-6 cells at different positions within the neuroectoderm (e.g., achaete is expressed in four clusters, in the ventral and dorsal columns of rows 3 and 7). Proneural genes promote the formation of neuroblasts, whereas Delta-Notch signaling inhibits neuroblast formation; the balance of proneural and Notch activity results in the formation of a single neuroblast from each cluster (for review, see Campos-Ortega 1993).What are the cues that specify correct neuroblast identity along the AP and DV axes? The segment polarity genes wingless, hedgehog, gooseberry, and engrailed are expressed in stripes in the neuroectoderm and specify the AP row identity of neuroblasts (Chu-LaGraff and Doe 1993;Zhang et al. 1994;Skeath et al. 1995;Bhat 1996;Matsuzaki and Saigo 1996;Bhat and Schedl 1997). Conditional inactivation (for wingless; Chu-LaGraff and Doe 1993) or misexpression (for gooseberry; Skeath et al. 1995) experiments show that segment polarity gene function is required in the neuroectoderm, prior to neuroblast delamination, for the proper specification of neuroblast identity.Less is known about how neuroectoderm and neuro-

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.