Experiments in both vertebrates and invertebrates have illustrated the competitive nature of growth and led to the idea that competition is a mechanism of regulating organ and tissue size. We have assessed competitive interactions between cells in a developing organ and examined their effect on its final size. We show that local expression of the Drosophila growth regulator dMyc, a homolog of the c-myc protooncogene, induces cell competition and leads to the death of nearby wild-type cells in developing wings. We demonstrate that cell competition is executed via induction of the proapoptotic gene hid and that both competition and hid function are required for the wing to reach an appropriate size when dMyc is expressed. Moreover, we provide evidence that reproducible wing size during normal development requires apoptosis. Modulating dmyc levels to create cell competition and hid-dependent cell death may be a mechanism used during normal development to control organ size.

Transcription factors of the Myc proto-oncogene family promote cell division, but how they do this is poorly understood. Here we address the functions of Drosophila Myc (dMyc) during development. Using mosaic analysis in the fly wing, we show that loss of dMyc retards cellular growth (accumulation of cell mass) and reduces cell size, whereas dMyc overproduction increases growth rates and cell size. dMyc-induced growth promotes G1/S progression but fails to accelerate cell division because G2/M progression is independently controlled by Cdc25/String. We also show that the secreted signal Wingless patterns growth in the wing primordium by modulating dMyc expression. Our results indicate that dMyc links patterning signals to cell division by regulating primary targets involved in cellular growth and metabolism.

Abstract. Cyclin proteins form complexes with members ofthe p34cdc 2 kinase family and they are essential components ofthe cell cycle regulatory machinery. They are thought to determine the timing of activation, the subcellular distribution, and/or the substrate specificity ofcdc2-related kinases, but their precise mode ofaction remains to be elucidated. Here we report the cloning and sequencing of avian cyclin B2. Based on the use of monospecific antibodies raised against bacterially expressed protein, we also describe the subcellular distribution of cyclin B2 in chick embryo fibroblasts and in DU249 hepatoma cells. By indirect immunofluorescence

The proteins encoded by the myc proto-oncogene family are involved in cell proliferation, apoptosis, differentiation, and neoplasia. Myc acts through dimerization with Max to bind DNA and activate transcription. Homologs of the myc and max genes were cloned from the fruit fly Drosophila melanogaster and their protein products (dMyc and dMax) were shown to heterodimerize, recognize the same DNA sequence as their vertebrate homologs, and activate transcription. The dMyc protein is likely encoded by the Drosophila gene diminutive (dm), a mutation in which results in small body size and female sterility caused by degeneration of the ovaries. These findings indicate a potential role for Myc in germ cell development and set the stage for genetic analysis of Myc and Max.

Transplantation experiments have shown that developing metazoan organs carry intrinsic information about their size and shape. Organ and body size are also sensitive to extrinsic cues provided by the environment, such as the availability of nutrients. The genetic and molecular pathways that contribute to animal size and shape are numerous, yet how they cooperate to control growth is mysterious. The recent identification and characterization of several mutations affecting growth in Drosophila melanogaster promises to provide insights. Many of these mutations affect the extrinsic control of animal size; others affect the organ-intrinsic control of pattern and size. In this review, we summarize the characteristics of some of these mutations and their roles in growth and size control. In addition, we speculate about possible connections between the extrinsic and intrinsic pathways controlling growth and pattern.

Pontin and Reptin are two closely related members of the AAA+ family of DNA helicases. They have roles in diverse cellular processes, including the response to DNA double-strand breaks and the control of gene expression. The two proteins share residence in different multiprotein complexes, such as the Tip60, Ino80, SRCAP and Uri1 complexes in animals, which are involved (directly or indirectly) in transcriptional regulation, but they also function independently from each other. Both Reptin and Pontin repress certain transcriptional targets of Myc, but only Reptin is required for the repression of specific ?-catenin and nuclear factor-?B targets. Here, I review recent studies that have addressed the mechanisms of transcriptional control by Pontin and Reptin. 1Trends in Cell Biology 2007, 17(4): 187-192. Control of transcription by Pontin and ReptinPeter Gallant Zoologisches Institut, Universität Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland; email: gallant@zool.unizh.ch; phone: +41446354812. AbstractPontin and Reptin are two closely related members of the AAA+ family of DNA helicases. They play roles in diverse cellular processes, including the response to DNA double-strand breaks and the control of gene expression. The two proteins share residence in different multi-protein complexes, such as the Tip60-, Ino80-, SRCAP-and Uri1-complexes in animals which are (directly or indirectly) involved in transcriptional regulation, but they also function independently from each other. Both Reptin and Pontin repress certain transcriptional targets of Myc, but only Reptin is required for the repression of specific β-Catenin and nuclear factor-κB targets. Here, I review recent studies that have addressed the mechanisms of transcriptional control by Pontin and Reptin.

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Myc proteins are powerful proto-oncoproteins and important promoters of growth and proliferation during normal development. They are thought to exercise their effects upon binding to their partner protein Max, and their activities are largely antagonized by complexes of Max with Mnt or an Mxd family protein. Although the biological functions of Myc, Mxd and Mnt have been intensively studied, comparatively little is known about the in vivo role of Max. Here we generate Max loss-of-function and reduction-of-function mutations in Drosophila melanogaster to address the contribution of Max to Myc-dependent growth control. We find that many biological activities of Myc do not, or only partly, require the association with Max--for example, the control of endoreplication and cell competition-and that a Myc mutant that does not interact with Max retains substantial biological activity. We further show that Myc can control RNA polymerase III independently of Max, which explains some of Myc's observed biological activities. These studies show the ability of Myc to function independently of Max in vivo and thus change the current model of Max network function.