Apoptosis and its molecular mediators, the caspases, have long been regarded as tumor suppressors and one hallmark of cancer is ‘Evading Apoptosis’. However, recent work has suggested that apoptotic caspases can also promote proliferation and tumor growth under certain conditions. How caspases promote proliferation and how cells are protected from the potentially harmful action of apoptotic caspases is largely unknown. Here, we show that although caspases are activated in a well-studied neoplastic tumor model in Drosophila, oncogenic mutations of the proto-oncogene Ras (RasV12) maintain tumorous cells in an ‘undead’-like condition and transform caspases from tumor suppressors into tumor promotors. Instead of killing cells, caspases now promote the generation of intra- and extracellular reactive oxygen species (ROS). One function of the ROS is the recruitment and activation of macrophage-like immune cells which in turn signal back to tumorous epithelial cells to activate oncogenic JNK signaling. JNK further promotes and amplifies caspase activity, thereby constituting a feedback amplification loop. Interfering with the amplification loop strongly reduces the neoplastic behavior of these cells and significantly improves organismal survival. In conclusion, RasV12-modified caspases initiate a feedback amplification loop involving tumorous epithelial cells and macrophage-like immune cells that is necessary for uncontrolled tumor growth and invasive behavior.

Apoptosis is prevalent during development of the central nervous system (CNS), yet very little is known about the signals that specify an apoptotic cell fate. In this paper, we examine the role of Numb/Notch signaling in the development of the serotonin lineage of Drosophila and show that it is necessary for regulating apoptosis. Our results indicate that when Numb inhibits Notch signaling, cells undergo neuronal differentiation, whereas cells that maintain Notch signaling initiate apoptosis. The apoptosis inhibitor p35 can counteract Notch-mediated apoptosis and rescue cells within the serotonin lineage that normally undergo apoptosis. Furthermore, we observe tumor-like overproliferation of cells in the CNS when Notch signaling is reduced. These data suggest that the distribution of Numb during terminal mitotic divisions of the CNS can distinguish between a neuronal cell fate and programmed cell death.

Presently there are no good assays for comparing somatic mutation frequencies and spectra between different vertebrate and invertebrate organisms. Here we describe a new lacZ mutation reporter system in D. melanogaster, which complements existing systems in the mouse. The results obtained with the new model indicate two-to threefold higher frequencies of spontaneous mutations than in the mouse, with most of the mutations characterized as large genome rearrangements.Mutations are the prime substrate for natural selection in creating a wide variety of species well adapted to their environment. Random mutations, however, have generally adverse effects and are the cause of heritable disease, cancer and, possibly, aging 1 . Somatic mutagenesis is difficult to study in higher organisms, with most assays being indirect and based on alterations in phenotypic characteristics, such as the mouse or D. melanogaster spot tests 2,3 . Direct methods are available, but they are restricted to point mutations in restriction enzyme recognition sites 4 . In the past, we have generated transgenic mouse models harboring chromosomally integrated lacZ-plasmid constructs that can be recovered into Escherichia coli for the subsequent quantification and sequence characterization of a broad range of spontaneous mutations. Such systems do not exist for invertebrates, and information as to how the spontaneous mutation burden in somatic tissues of such organisms differs from those in mammals is absent.Here we generated a transgenic D. melanogaster animal model for studying a broad range of somatic mutations by inserting a lacZ plasmid reporter construct (pUR288-S; Supplementary Methods online and Supplementary Fig. 1 online) in a D. melanogaster chromosome as part of a pCasper transformation vector (Fig. 1). We made a total of six lines (2, 4, 5, 7, 9 and 11), each harboring one copy of the plasmid construct (Fig. 1a) integrated at a particular Correspondence should be addressed to J.V. (jvijg@buckinstitute.org). Note: Supplementary information is available on the Nature Methods website. COMPETING INTERESTS STATEMENTThe authors declare no competing financial interests. NIH Public Access

Autophagy is a catabolic process that has been implicated as both a tumor suppressor and in tumor progression. Here, we investigate this dichotomy in cancer biology by studying the influence of altered autophagy in Drosophila models of tissue overgrowth. We find that the impact of altered autophagy depends on both genotype and cell type. As previously observed in mammals, decreased autophagy suppresses Ras-induced eye epithelial overgrowth. By contrast, autophagy restricts epithelial overgrowth in a Notch-dependent eye model. Even though decreased autophagy did not influence Hippo pathway-triggered overgrowth, activation of autophagy strongly suppresses this eye epithelial overgrowth. Surprisingly, activation of autophagy enhanced Hippo pathway-driven overgrowth in glia cells. These results indicate that autophagy has different influences on tissue growth in distinct contexts, and highlight the importance of understanding the influence of autophagy on growth to augment a rationale therapeutic strategy.

Brain morphology, with special attention to the three dimensional form of the corpora pedunculata, was studied in thirteen species of ants, representing four subfamilies of Formicidae. The results can be summarized as follows. (1) The neural systems processing optic and olfactory information differ in the evolutionary history among the studied taxa. A positive correlation can be demonstrated in the phylogenetic history of the corpora pedunculata, central body, cerebral bridge and olfactory lobe, but not the optic lobe. Ant species with very large eyes and thus, probably, highly developed vision, show gigantic optic lobes, with no exaggeration of any other brain structure. (2) More social species have more complex chemical communication systems and better developed corpora pedunculata (more surface in foldings of the calyces) and olfactory lobes; however, this tendency seems to reverse in highly social species with a sophisticated polymorphic caste system: individuals of these species are generally less developed neurally. (3) There are differences between the form of the internal and external calyces of the corpora pedunculata, and these differences are proportionately more pronounced in species with complex social organization. (4) Individuals from different worker castes of the same species differ in their brain morphology, but each species shows a different pattern of variation among their castes. (5) Brain structure shows characteristic marks due to the different phylogenetic developments in the taxa studied. For example the trends in brain volume-body size ratio are different for the various subfamilies, suggesting a divergent phylogenetic history.

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