title: Regulation of temporal identity transitions in Drosophila neuroblasts.
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.
authors.affiliation: Institutes of Neuroscience and Molecular Biology, Howard Hughes Medical Institute, University of Oregon 1254, Eugene, Oregon 97403, USA.
authors.forename: Ruth
authors.initials: R
authors.lastname: Grosskortenhaus
authors.forename: Bret J
authors.initials: BJ
authors.lastname: Pearson
authors.forename: Amanda
authors.initials: A
authors.lastname: Marusich
authors.forename: Chris Q
authors.initials: CQ
authors.lastname: Doe
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D019521:Body Patterning; D002453:Cell Cycle; D002490:Central Nervous System / Q000196:embryology; D048749:Cytokinesis; D004268:DNA-Binding Proteins / Q000235:genetics; D004330:Drosophila / Q000196:embryology* / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D018398:Homeodomain Proteins / Q000235:genetics; D051741:Kruppel-Like Transcription Factors; D008959:Models, Neurological; D009474:Neurons / Q000166:cytology*; D050809:POU Domain Factors; D012097:Repressor Proteins / Q000235:genetics; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology; D014157:Transcription Factors / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; C497244:Kr protein, Drosophila; D051741:Kruppel-Like Transcription Factors; D050809:POU Domain Factors; D012097:Repressor Proteins; D014157:Transcription Factors; C110593:cas protein, Drosophila; C061245:hb protein, Drosophila; C104121:nub protein, Drosophila