Combinatorial transcriptional regulation: the interaction of transcription factors and cell signaling molecules with homeodomain proteins in Drosophila development

Crit Rev Eukaryot Gene Expr. 2001;11(1-3):145-71.


Patterning and cell fate specification during development require complex interplay among multiple families of transcription factors to establish, maintain, and coordinate transcriptional cascades. During these processes, homeodomain proteins and cell signaling proteins cooperate to generate tissue-and stage-specific responses. This review of physical and genetic interactions in Drosophila melanogaster development highlights the cross-talk among these protein families. Protein-protein association can modulate regulation by both signal transduction-regulated transcription factors and homeodomain proteins, as observed in Drosophila and other organisms. Enhancers or genes regulated by multiple transcription factors provide opportunities for protein-protein binding to modulate transcription factor function. Combinatorial regulation of several enhancers by homeodomain proteins and cell signaling-regulated transcription factors is discussed; detailed maps of the genetic interactions that pattern the embryonic midgut and the larval wing imaginal disc are used to illustrate the multiplicity of potential protein-protein interactions. These interactions potentially provide direct mechanisms for communication between transcription factors as well as for generating the requisite functional specificity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Cell Lineage
  • Drosophila Proteins / biosynthesis
  • Drosophila Proteins / genetics
  • Drosophila Proteins / physiology*
  • Drosophila melanogaster / embryology
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / growth & development
  • Embryo, Nonmammalian
  • Enhancer Elements, Genetic
  • Gene Expression Regulation, Developmental*
  • Genes, Homeobox
  • Genes, Insect
  • Genes, Regulator
  • Homeodomain Proteins / physiology*
  • Intestines / embryology
  • Larva
  • Macromolecular Substances
  • Morphogenesis
  • Multigene Family
  • Signal Transduction / physiology*
  • Transcription Factors / classification
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • Transcription, Genetic / genetics
  • Transcription, Genetic / physiology*
  • Wings, Animal / growth & development


  • Drosophila Proteins
  • Homeodomain Proteins
  • Macromolecular Substances
  • Transcription Factors