Reference Report

Reference
Citation	Butchar, J.P., Cain, D., Manivannan, S.N., McCue, A.D., Bonanno, L., Halula, S., Truesdell, S., Austin, C.L., Jacobsen, T.L., Simcox, A. (2012). New negative feedback regulators of egfr signaling in Drosophila. Genetics 191(4): 1213--1226. (Export to RIS)
FlyBase ID	FBrf0219175
Publication Type	Research paper
PubMed ID	22595244
PubMed Abstract	The highly conserved epidermal growth factor receptor (Egfr) pathway is required in all animals for normal development and homeostasis; consequently, aberrant Egfr signaling is implicated in a number of diseases. Genetic analysis of Drosophila melanogaster Egfr has contributed significantly to understanding this conserved pathway and led to the discovery of new components and targets. Here we used microarray analysis of third instar wing discs, in which Egfr signaling was perturbed, to identify new Egfr-responsive genes. Upregulated transcripts included five known targets, suggesting the approach was valid. We investigated the function of 29 previously uncharacterized genes, which had pronounced responses. The Egfr pathway is important for wing-vein patterning and using reverse genetic analysis we identified five genes that showed venation defects. Three of these genes are expressed in vein primordia and all showed transcriptional changes in response to altered Egfr activity consistent with being targets of the pathway. Genetic interactions with Egfr further linked two of the genes, Sulfated (Sulf1), an endosulfatase gene, and CG4096, an A Disintegrin And Metalloproteinase with ThromboSpondin motifs (ADAMTS) gene, to the pathway. Sulf1 showed a strong genetic interaction with the neuregulin-like ligand vein (vn) and may influence binding of Vn to heparan-sulfated proteoglycans (HSPGs). How Drosophila Egfr activity is modulated by CG4096 is unknown, but interestingly vertebrate EGF ligands are regulated by a related ADAMTS protein. We suggest Sulf1 and CG4096 are negative feedback regulators of Egfr signaling that function in the extracellular space to influence ligand activity.
DOI	10.1534/genetics.112.141093
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Language of Publication	English
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Publication Type	Journal
Abbreviation	Genetics
Title	Genetics
Publication Year	1916-
ISBN/ISSN	0016-6731
Data from Reference
Aberrations (1)
	Df(2R)Egfr3
Alleles (36)
	btl::Egfr^{Scer\UAS.T:λ\cI-DD} CG3857^KK110209 CG4096^KK108644 CG4382^GD5236 CG5800^KK102565 CG6234^KK105328 CG6234^Scer\UAS.cBa CG7860^KK107662 CG10200^KK112899 CG17746^KK105177 CG34398^KK114488 Cyp4e2^KK104577 Cypl^KK107406 Egfr^{DN.Scer\UAS.cBa} Egfr^E1 ImpE1^KK111088 Krn²⁷ nyo^KK111035 pnt^Δ88 Ras85D^e1B regucalcin^KK112078 Scer\GAL4^71B Scer\GAL4^Act5C.PU Scer\GAL4^en-e16E Scer\GAL4^sd.PU Scer\GAL4^vn-GAL4 SP1029^KK110719 spi¹ Sulf1^{ER.Scer\UAS.T:Uuuu\KDEL} Sulf1^{Golgi.Scer\UAS.T:Hsap\GALNT3} Sulf1^Scer\UAS.cBa Sulf1^Scer\UAS.cKa vn^ddd-3 vn^GAL4 vn^L6 vn^Scer\UAS.cSa
Constructs (12)
	P{Act5C-GAL4.U} P{GAL4} P{KK108644} P{sd-GAL4.U} P{UAS-CG6234.B} P{UAS-Egfr.DN.B} P{UAS-Egfr.λtop} P{UAS-Sulf1.B} P{UAS-Sulf1.K} P{UAS-Sulf1-ER} P{UAS-Sulf1-Golgi} P{UAS-vn.S}
Genes (59)
	Ance AnxB10 aos bel BM-40-SPARC btl::Egfr CG3857 CG4096 CG4210 CG4382 CG5326 CG5800 CG6234 CG7860 CG9691 CG9914 CG10200 CG10359 CG11899 CG13053 CG17746 CG31075 CG34398 CG42748 corto Cyp4e2 Cypl Ect3 Egfr egg eIF5B Fbp2 GstE1 Idgf4 ImpE1 Krn mask Mgstl Mkp3 nyo obst-B pk pnt qkr58E-1 Ras85D regucalcin rho rl salm Scer\GAL4 Sod3 SP1029 spg spi sty Sulf1 tou vn vvl
Insertions (3)
	P{en2.4-GAL4}e16E P{GAL4}vn^GAL4 P{GawB}71B
Natural transposons (1)
	P-element