Affecting Rhomboid-3 function causes a dilated heart in adult Drosophila.
Abstract
Drosophila is a well recognized model of several human diseases, and recent investigations
have demonstrated that Drosophila can be used as a model of human heart failure. Previously,
we described that optical coherence tomography (OCT) can be used to rapidly examine
the cardiac function in adult, awake flies. This technique provides images that are
similar to echocardiography in humans, and therefore we postulated that this approach
could be combined with the vast resources that are available in the fly community
to identify new mutants that have abnormal heart function, a hallmark of certain cardiovascular
diseases. Using OCT to examine the cardiac function in adult Drosophila from a set
of molecularly-defined genomic deficiencies from the DrosDel and Exelixis collections,
we identified an abnormally enlarged cardiac chamber in a series of deficiency mutants
spanning the rhomboid 3 locus. Rhomboid 3 is a member of a highly conserved family
of intramembrane serine proteases and processes Spitz, an epidermal growth factor
(EGF)-like ligand. Using multiple approaches based on the examination of deficiency
stocks, a series of mutants in the rhomboid-Spitz-EGF receptor pathway, and cardiac-specific
transgenic rescue or dominant-negative repression of EGFR, we demonstrate that rhomboid
3 mediated activation of the EGF receptor pathway is necessary for proper adult cardiac
function. The importance of EGF receptor signaling in the adult Drosophila heart underscores
the concept that evolutionarily conserved signaling mechanisms are required to maintain
normal myocardial function. Interestingly, prior work showing the inhibition of ErbB2,
a member of the EGF receptor family, in transgenic knock-out mice or individuals that
received herceptin chemotherapy is associated with the development of dilated cardiomyopathy.
Our results, in conjunction with the demonstration that altered ErbB2 signaling underlies
certain forms of mammalian cardiomyopathy, suggest that an evolutionarily conserved
signaling mechanism may be necessary to maintain post-developmental cardiac function.
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https://hdl.handle.net/10161/4471Published Version (Please cite this version)
10.1371/journal.pgen.1000969Publication Info
Yu, L; Lee, T; Lin, N; & Wolf, MJ (2010). Affecting Rhomboid-3 function causes a dilated heart in adult Drosophila. PLoS genetics, 6(5). pp. e1000969. 10.1371/journal.pgen.1000969. Retrieved from https://hdl.handle.net/10161/4471.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Matthew Joseph Wolf
Associate Professor of Medicine
My research interests focus on the identification of genes and pathways that cause
or modify cardiac hypertrophy and heart failure. Using the unique resources that are
available to the Drosophila genetics/genomics community, my laboratory has developed
strategies to examine cardiac function in fruit flies. Genetic screens of Drosophila
have identified a variety of mutants that potentially influence cardiac function.
Discoveries of new genes in fruit fly models of cardiovascular disease are
This author no longer has a Scholars@Duke profile, so the information shown here reflects
their Duke status at the time this item was deposited.

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