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.

Individual neural progenitors generate different cell types in a reproducible order in the retina, cerebral cortex and probably in the spinal cord. It is unknown how neural progenitors change over time to generate different cell types. It has been proposed that progenitors undergo progressive restriction or transit through distinct competence states; however, the underlying molecular mechanisms remain unclear. Here we investigate neural progenitor competence and temporal identity using an in vivo genetic system--Drosophila neuroblasts--where the Hunchback transcription factor is necessary and sufficient to specify early-born cell types. We show that neuroblasts gradually lose competence to generate early-born fates in response to Hunchback, similar to progressive restriction models, and that competence to acquire early-born fates is present in mitotic precursors but is lost in post-mitotic neurons. These results match those observed in vertebrate systems, and establish Drosophila neuroblasts as a model system for the molecular genetic analysis of neural progenitor competence and plasticity.

The origin of new morphological characters is a long-standing problem in evolutionary biology. Novelties arise through changes in development, but the nature of these changes is largely unknown. In butterflies, eyespots have evolved as new pattern elements that develop from special organizers called foci. Formation of these foci is associated with novel expression patterns of the Hedgehog signaling protein, its receptor Patched, the transcription factor Cubitus interruptus, and the engrailed target gene that break the conserved compartmental restrictions on this regulatory circuit in insect wings. Redeployment of preexisting regulatory circuits may be a general mechanism underlying the evolution of novelties.