Regulation of temporal identity transitions in Drosophila neuroblasts

Dev Cell. 2005 Feb;8(2):193-202. doi: 10.1016/j.devcel.2004.11.019.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Body Patterning
  • Cell Cycle
  • Central Nervous System / embryology
  • Cytokinesis
  • DNA-Binding Proteins / genetics
  • Drosophila / embryology*
  • Drosophila / genetics
  • Drosophila Proteins / genetics
  • Gene Expression Regulation, Developmental
  • Genes, Insect
  • Homeodomain Proteins / genetics
  • Kruppel-Like Transcription Factors
  • Models, Neurological
  • Neurons / cytology*
  • POU Domain Factors
  • Repressor Proteins / genetics
  • Signal Transduction
  • Stem Cells / cytology
  • Transcription Factors / genetics

Substances

  • DNA-Binding Proteins
  • Drosophila Proteins
  • Homeodomain Proteins
  • Kr protein, Drosophila
  • Kruppel-Like Transcription Factors
  • POU Domain Factors
  • Repressor Proteins
  • Transcription Factors
  • cas protein, Drosophila
  • hb protein, Drosophila
  • nub protein, Drosophila