Down-regulation of Notch target gene expression by Suppressor of deltex.
In Drosophila, Suppressor of deltex (Su(dx)) mutations display a wing vein gap phenotype resembling that of Notch gain of function alleles. The Su(dx) protein may therefore act as a negative regulator of Notch but its activity on actual Notch signalling levels has not been demonstrated. Here we show that Su(dx) does regulate the level of Notch signalling in vivo, upstream of Notch target genes and in different developmental contexts, including a previously unknown role in leg joint formation. Overexpression of Su(dx) was capable of blocking both the endogenous activity of Notch and the ectopic Notch signalling induced by the overexpression of Deltex, an intracellular Notch binding protein. In addition, using the conditional phenotype of the Su(dx)(sp) allele, we show that loss of Su(dx) activity is rapidly followed by an up-regulation of E(spl)mbeta expression, the immediate target of Notch signal activation during wing vein development. While Su(dx) adult wing vein phenotypes are quite mild, only affecting the distal tips of the veins, we show that the initial consequence of loss of Su(dx) activity is more severe than previously thought. Using a time-course experiment we show that the phenotype is buffered by feedback regulation illustrating how signalling networks can make development robust to perturbation.
Mazaleyrat
Sabine L
SL
University of Manchester, School of Biological Sciences, Stopford Building, Oxford Road, Manchester, M13 9PT UK.
Fostier
Maggy
M
Wilkin
Marian B
MB
Aslam
Hanna
H
Evans
Dana A P
DA
Cornell
Michael
M
Baron
Martin
M
D000483:Alleles; D000818:Animals; D030801:Animals, Genetically Modified; D015536:Down-Regulation; D004330:Drosophila / Q000235:genetics* / Q000254:growth & development* / Q000378:metabolism; D029721:Drosophila Proteins; D005121:Extremities / Q000254:growth & development; D005246:Feedback; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D007596:Joints / Q000254:growth & development; D008025:Ligases / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D010641:Phenotype; D051880:Receptors, Notch; D015398:Signal Transduction; D044767:Ubiquitin-Protein Ligases; D014921:Wings, Animal / Q000254:growth & development
D029721:Drosophila Proteins; D008565:Membrane Proteins; C497759:N protein, Drosophila; D051880:Receptors, Notch; C119838:Su(dx) protein, Drosophila; D044767:Ubiquitin-Protein Ligases; D008025:Ligases