Reference Report

Reference
Citation	Kim, I.M., Wolf, M.J., Rockman, H.A. (2010). Gene deletion screen for cardiomyopathy in adult Drosophila identifies a new notch ligand. Circulation Res. 106(7): 1233--1243. (Export to RIS)
FlyBase ID	FBrf0210603
Publication Type	Research paper
PubMed ID	20203305
PubMed Abstract	Drosophila has been recognized as a model to study human cardiac diseases.Despite these findings, and the wealth of tools that are available to the fly community, forward genetic screens for adult heart phenotypes have been rarely performed because of the difficulty in accurately measuring cardiac function in adult Drosophila.Using optical coherence tomography to obtain real-time analysis of cardiac function in awake Drosophila, we performed a genomic deficiency screen in adult flies. Based on multiple complementary approaches, we identified CG31665 as a novel gene causing dilated cardiomyopathy. CG31665, which we name weary (wry), has structural similarities to members of the Notch family. Using cell aggregation assays and gamma-secretase inhibitors we show that Wry is a novel Notch ligand that can mediate cellular adhesion with Notch expressing cells and transactivates Notch to promote signaling and nuclear transcription. Importantly, Wry lacks a DSL (Delta-Serrate-Lag) domain that is common feature to the other Drosophila Notch ligands. We further show that Notch signaling is critically important for the maintenance of normal heart function of the adult fly.In conclusion, we identify a previously unknown Notch ligand in Drosophila that when deleted causes cardiomyopathy. Our study suggests that Notch signaling components may be a therapeutic target for dilated cardiomyopathy.
DOI	10.1161/CIRCRESAHA.109.213785
Related Publication(s)
Recent Updates
Description	What does this section display? This section contains items that were added to this record for each release. It currently only tracks new links between this FlyBase report and other FlyBase data classes (e.g. genes, references, stocks) or controlled vocabulary terms (e.g. GO, anatomy terms). What does this section not display? This section does not currently display links that were removed or gene model changes.
Update Feed	Click the icon below to subscribe to this FlyBase record and receive updates automatically through your feed reader.
FB2013_03
FB2013_02
All updates	Click here to see a list of all updates to this record from FB2010_08 and on.
Associated Information
Comments
Associated Files
Other Information
Secondary IDs
Language of Publication	English
Additional Languages of Abstract
Also Published As
Parent Publication
Publication Type	Journal
Abbreviation	Circulation Res.
Title	Circulation Research
Publication Year	1953-
ISBN/ISSN	0009-7330
Data from Reference
Aberrations (6)
	Df(2L)Exel6005 Df(2L)Exel6006 Df(2L)Exel7002 Df(2L)Exel7007 Df(2L)Exel8003 Df(2L)Exel8005
Alleles (18)
	CG31663^MB00634 Dl^D.Scer\UAS Dl^Scer\UAS.cDa H^Scer\UAS.cGa N^Scer\UAS.cMa Scer\GAL4^Act5C.PU Scer\GAL4^hs.PB Scer\GAL4^tin.CΔ4 Scer\GAL4^vg.MQ.Exel Scer\GAL80^ts.αTub84B Ser^DN.Scer\UAS Ser^Scer\UAS.cSa Ser^VDRC.cUa Su(H)^Scer\UAS.cGa wry^f00122 wry^MB00103 wry^Scer\UAS.cKa wry^VDRC.cUa
Constructs (15)
	P{Act5C-GAL4.U} P{GAL4-Hsp70.PB} P{tinC-Gal4.Δ4} P{tubP-GAL80^ts} P{UAS-Dl.D} P{UAS-Dl.DN} P{UAS-H.G} P{UAS-N^full} P{UAS-Ser.DN} P{UAS-Ser.mg5603} P{UAS-Su(H).G} P{UAS-wry.K} P{VDRC.wry.U} P{VDRC-Ser.U} P{vgMQ-GAL4.Exel}
Genes (10)
	c-cup CG31663 Dl H N Scer\GAL4 Scer\GAL80 Ser Su(H) wry
Insertions (4)
	Mi{ET1}CG31663^MB00634 Mi{ET1}wry^MB00103 PBac{RB}e02146 PBac{WH}wry^f00122
Natural transposons (1)
	P-element