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

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.