Self-modulation of Notch signaling during ommatidial development via the Roughened eye transcriptional repressor.
The Notch (N) signaling pathway is involved in a vast number of patterning processes in all metazoans. The regulation of the core N pathway is largely understood, but little is known about fine-tuning modulatory effects. Here, we address the role of Drosophila Krüppel-family Zn-finger transcription factor roughened eye (roe) in the context of N signaling. We demonstrate that during eye patterning, N signaling regulates the expression of roe. In turn, Roe negatively modulates the expression of target genes of N-signaling activation. In the absence of roe function, expression of N target genes is elevated and the resulting phenotypes during patterning of the retina are similar to those of N gain-of-function scenarios. Importantly, our data show that Roe binds regulatory DNA sequences of N target genes of the E(spl)-complex both in vitro and in vivo, independently of Su(H)-DNA interaction. Thus, our data suggest that Roe acts as a transcriptional repressor in a negative-feedback loop of the N pathway.
del Alamo
David
D
Department of Developmental and Regenerative Biology, Mount Sinai School of Medicine, 1 Gustave L. Levy Place, New York, NY 10029, USA.
Mlodzik
Marek
M
D000818:Animals; D019521:Body Patterning; D002465:Cell Movement; D002999:Clone Cells; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000196:embryology*; D005123:Eye / Q000166:cytology / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D011485:Protein Binding; D051880:Receptors, Notch / Q000378:metabolism*; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
D029721:Drosophila Proteins; D051880:Receptors, Notch; D012097:Repressor Proteins; D014157:Transcription Factors; C450830:roughened protein, Drosophila