The function and regulation of cut expression on the wing margin of Drosophila: Notch, Wingless and a dominant negative role for Delta and Serrate.
We have investigated the role of the Notch and Wingless signaling pathways in the maintenance of wing margin identity through the study of cut, a homeobox-containing transcription factor and a late-arising margin-specific marker. By late third instar, a tripartite domain of gene expression can be identified about the dorsoventral compartment boundary, which marks the presumptive wing margin. A central domain of cut- and wingless-expressing cells are flanked on the dorsal and ventral side by domains of cells expressing elevated levels of the Notch ligands Delta and Serrate. We show first that cut acts to maintain margin wingless expression, providing a potential explanation of the cut mutant phenotype. Next, we examined the regulation of cut expression. Our results indicate that Notch, but not Wingless signaling, is autonomously required for cut expression. Rather, Wingless is required indirectly for cut expression; our results suggest this requirement is due to the regulation by wingless of Delta and Serrate expression in cells flanking the cut and wingless expression domains. Finally, we show that Delta and Serrate play a dual role in the regulation of cut and wingless expression. Normal, high levels of Delta and Serrate can trigger cut and wingless expression in adjacent cells lacking Delta and Serrate. However, high levels of Delta and Serrate also act in a dominant negative fashion, since cells expressing such levels cannot themselves express cut or wingless. We propose that the boundary of Notch ligand along the normal margin plays a similar role as part of a dynamic feedback loop that maintains the tripartite pattern of margin gene expression.
Micchelli
C A
CA
Department of Zoology, University of Wisconsin, Madison 53706, USA.
Rulifson
E J
EJ
Blair
S S
SS
D000818:Animals; D002135:Calcium-Binding Proteins; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000196:embryology* / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D005799:Genes, Dominant; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008565:Membrane Proteins / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009687:Nuclear Proteins / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051880:Receptors, Notch; D012097:Repressor Proteins / Q000502:physiology; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction; D014157:Transcription Factors; D014921:Wings, Animal / Q000196:embryology*; D051155:Wnt1 Protein
D002135:Calcium-Binding Proteins; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; C497759:N protein, Drosophila; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D051880:Receptors, Notch; D012097:Repressor Proteins; C000606278:Ser protein, Drosophila; D000072099:Serrate-Jagged Proteins; D014157:Transcription Factors; D051155:Wnt1 Protein; C066381:ct protein, Drosophila; C074622:wg protein, Drosophila