Abstract
Temporal patterning is an important aspect of embryonic development, but the underlying molecular mechanisms are not well understood. Drosophila neuroblasts are an excellent model for studying temporal identity: they sequentially express four genes (hunchback --> Kruppel --> pdm1 --> castor) whose temporal regulation is essential for generating neuronal diversity. Here we show that hunchback --> Kruppel timing is regulated transcriptionally and requires neuroblast cytokinesis, consistent with asymmetric partitioning of transcriptional regulators during neuroblast division or feedback signaling from the neuroblast progeny. Surprisingly, Kruppel --> pdm1 --> castor timing occurs normally in isolated or G(2)-arrested neuroblasts, and thus involves a neuroblast-intrinsic timer. Finally, we find that Hunchback potently regulates the neuroblast temporal identity timer: prolonged Hunchback expression keeps the neuroblast "young" for multiple divisions, and subsequent downregulation allows resumption of Kruppel --> pdm1 --> castor expression and the normal neuroblast lineage. We conclude that two distinct "timers" regulate neuroblast gene expression: a hunchback --> Kruppel timer requiring cytokinesis, and a Kruppel --> pdm1 --> castor timer which is cell cycle independent.
