Regulation of temporal identity transitions in Drosophila neuroblasts.
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.
Grosskortenhaus
Ruth
R
Institutes of Neuroscience and Molecular Biology, Howard Hughes Medical Institute, University of Oregon 1254, Eugene, Oregon 97403, USA.
Pearson
Bret J
BJ
Marusich
Amanda
A
Doe
Chris Q
CQ
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
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