Drosophila, the golden bug, emerges as a tool for human genetics.

Section of Cell and Developmental Biology, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92039, USA.
Nature Reviews Genetics (Impact Factor: 39.79). 02/2005; 6(1):9-23. DOI: 10.1038/nrg1503
Source: PubMed

ABSTRACT Drosophila melanogaster is emerging as one of the most effective tools for analyzing the function of human disease genes, including those responsible for developmental and neurological disorders, cancer, cardiovascular disease, metabolic and storage diseases, and genes required for the function of the visual, auditory and immune systems. Flies have several experimental advantages, including their rapid life cycle and the large numbers of individuals that can be generated, which make them ideal for sophisticated genetic screens, and in future should aid the analysis of complex multigenic disorders. The general principles by which D. melanogaster can be used to understand human disease, together with several specific examples, are considered in this review.

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    ABSTRACT: Apoptosis is a conserved process aimed to eliminate unwanted cells. Key molecules are a group of proteases called caspases that cleave vital proteins, leading to the death of cells. In Drosophila the apoptotic pathway is usually represented as a cascade of events in which an initial stimulus activates pro- apoptotic genes, which in turn activate caspases. In stress-induced apoptosis the Dp53 gene and the JNK pathway initially activate the pro-apoptotic genes. Here we demonstrate that Dp53 and JNK also function downstream of pro-apoptotic genes and the initiator caspase 9/Dronc and that they establish a feedback loop that amplifies the initial apoptotic stimulus. This loop plays a key function in the apoptotic response because in its absence there is a dramatic decrease in the amount of cell death after a pulse of pro-apoptotic proteins. Thus our results indicate that most of the apoptosis in Drosophila is mediated by the Dp53/JNK loop. Furthermore, they also demonstrate a mechanism of mutual activation of pro-apoptotic genes. Apoptosis is a mechanism of tumour suppression. Our results place the pro-apoptotic, and hence anti-tumorigenic, activities of p53 and JNK in a new frame, downstream of caspase function. In addition, we show that a subproduct of sustained JNK activity in apoptotic cells is the emission of the mitogens Wg and Dpp.
    01/2011, Degree: PhD, Supervisor: Gines Morata
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    ABSTRACT: The discovery that mammalian cells can survive late-stage apoptosis challenges the general assumption that active caspases are markers of impending death. However, tools have not been available to track healthy cells that have experienced caspase activity at any time in the past. Therefore, to determine if cells in whole animals can undergo reversal of apoptosis, known as anastasis, we developed a dual color CaspaseTracker system for Drosophila to identify cells with ongoing or past caspase activity. Transient exposure of healthy females to environmental stresses such as cold shock or starvation activated the CaspaseTracker coincident with caspase activity and apoptotic morphologies in multiple cell types of developing egg chambers. Importantly, when stressed flies were returned to normal conditions, morphologically healthy egg chambers and new progeny flies were labeled by the biosensor, suggesting functional recovery from apoptotic caspase activation. In striking contrast to developing egg chambers, which lack basal caspase biosensor activation under normal conditions, many adult tissues of normal healthy flies exhibit robust caspase biosensor activity in a portion of cells, including neurons. The widespread persistence of CaspaseTracker-positivity implies that healthy cells utilize active caspases for non-apoptotic physiological functions during and after normal development.
    Scientific Reports 03/2015; 5:9015. DOI:10.1038/srep09015 · 5.08 Impact Factor
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    03/2015; 2(1):2-16. DOI:10.3390/jcdd2010002


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