Reference Report

Reference
Citation	Charroux, B., Freeman, M., Kerridge, S., Baonza, A. (2006). Atrophin contributes to the negative regulation of epidermal growth factor receptor signaling in Drosophila. Dev. Biol. 291(2): 278--290. (Export to RIS)
FlyBase ID	FBrf0190100
Publication Type	Research paper
PubMed ID	16445904
PubMed Abstract	Dentato-rubral and pallido-luysian atrophy (DRPLA) is a dominant, progressive neurodegenerative disease caused by the expansion of polyglutamine repeats within the human Atrophin-1 protein. Drosophila Atrophin and its human orthologue are thought to function as transcriptional co-repressors. Here, we report that Drosophila Atrophin participates in the negative regulation of Epidermal Growth Factor Receptor (EGFR) signaling both in the wing and the eye imaginal discs. In the wing pouch, Atrophin loss of function clones induces cell autonomous expression of the EGFR target gene Delta, and the formation of extra vein tissue, while overexpression of Atrophin inhibits EGFR-dependent vein formation. In the eye, Atrophin cooperates with other negative regulators of the EGFR signaling to prevent the differentiation of surplus photoreceptor cells and to repress Delta expression. Overexpression of Atrophin in the eye reduces the EGFR-dependent recruitment of cone cells. In both the eye and wing, epistasis tests show that Atrophin acts downstream or in parallel to the MAP kinase rolled to modulate EGFR signaling outputs. We show that Atrophin genetically cooperates with the nuclear repressor Yan to inhibit the EGFR signaling activity. Finally, we have found that expression of pathogenic or normal forms of human Atrophin-1 in the wing promotes wing vein differentiation and acts as dominant negative proteins inhibiting endogenous fly Atrophin activity.
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Language of Publication	English
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Publication Type	Journal
Abbreviation	Dev. Biol.
Title	Developmental Biology
Publication Year	1959-
ISBN/ISSN	0012-1606
Data from Reference
Alleles (30)
	aop^Scer\UAS.cRa aos^GMR.PC aos^Δ7 btl::Egfr^{Scer\UAS.T:λ\cI-DD} cic^D49 Egfr^DN.Scer\UAS Gug³⁵ Gug^1207D6 Gug⁰³⁹²⁸ Gug¹⁴⁹⁶⁷ Gug^Scer\UAS.cCa Gug^{Ubi-p63E.T:Avic\GFP} Hsap\ATN1^{N917.26Q.Scer\UAS} Hsap\ATN1^{N917.65Q.Scer\UAS} pnt¹²⁷⁷ pnt⁰⁷⁸²⁵ pnt^Δ88 rho^7M43 rho^hs.sev rho^PΔ5 rl^Sem ru¹ Scer\GAL4^arm.PS Scer\GAL4^Bx-MS1096 Scer\GAL4^C-580 Scer\GAL4^dpp.blk1 Scer\GAL4^GMR.PF sty^Δ5 vn¹⁰⁵⁶⁷ w^+mC
Constructs (13)
	P{GAL4-arm.S} P{GAL4-dpp.blk1} P{GAL4-ninaE.GMR} P{GMR-argos.C} P{lacW} P{UAS-aop.WT} P{UAS-ATN1.N917.26Q} P{UAS-ATN1.N917.65Q} P{UAS-Atro.C} P{UAS-Egfr.DN} P{UAS-Egfr.λtop} P{Ubi-Atro.GFP} P{ve^hs.sev}
Genes (20)
	aop aos arm ato btl::Egfr cic Dl Egfr elav Gug Hsap\ATN1 mwh pnt rho rl ru Scer\GAL4 sty vn w
Insertions (5)
	P{GawB}Bx^MS1096 P{GawB}C-580 P{lacW}Gug¹⁴⁹⁶⁷ P{lacW}pnt¹²⁷⁷ P{PZ}Gug⁰³⁹²⁸
Natural transposons (1)
	P-element