Integration of Insulin receptor/Foxo signaling and dMyc activity during muscle growth regulates body size in<i>Drosophila</i>

Demontis, Fabio; Perrimon, Norbert

doi:10.1242/dev.027466

Cited by 173 publications

(204 citation statements)

References 85 publications

(118 reference statements)

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“…Ultimately, adult body size for D. melanogaster is determined by the size of the larva when it ceases feeding and enters metamorphosis, and largely by larval muscle size. Demontis and Perrimon (2009) showed that muscle size variation linked to modified insulin/TOR signaling affected adult size. Moreover, they showed that increased size occurred through increasing both nuclei number and DNA content of each individual nucleus (ploidy) through increased endoreplication, in addition to behavioral responses that modulate feeding and nutritional uptake (Conlon and Raff 1999).…”

Section: Discussionmentioning

confidence: 99%

Life history evolution and cellular mechanisms associated with increased size in high‐altitude Drosophila

Lack

Yassin

Sprengelmeyer

et al. 2016

Ecology and Evolution

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Understanding the physiological and genetic basis of growth and body size variation has wide‐ranging implications, from cancer and metabolic disease to the genetics of complex traits. We examined the evolution of body and wing size in high‐altitude Drosophila melanogaster from Ethiopia, flies with larger size than any previously known population. Specifically, we sought to identify life history characteristics and cellular mechanisms that may have facilitated size evolution. We found that the large‐bodied Ethiopian flies laid significantly fewer but larger eggs relative to lowland, smaller‐bodied Zambian flies. The highland flies were found to achieve larger size in a similar developmental period, potentially aided by a reproductive strategy favoring greater provisioning of fewer offspring. At the cellular level, cell proliferation was a strong contributor to wing size evolution, but both thorax and wing size increases involved important changes in cell size. Nuclear size measurements were consistent with elevated somatic ploidy as an important mechanism of body size evolution. We discuss the significance of these results for the genetic basis of evolutionary changes in body and wing size in Ethiopian D. melanogaster.

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Section: Discussionmentioning

confidence: 99%

Life history evolution and cellular mechanisms associated with increased size in high‐altitude Drosophila

Lack

Yassin

Sprengelmeyer

et al. 2016

Ecology and Evolution

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“…Consequently, the pathways regulating cellular growth play important roles in the control of endoreplication (Demontis and Perrimon, 2009;Pierce et al, 2008;Steiger et al, 2008). But what might be the advantages of cell growth mediated via polyploidy?…”

Section: Consequences Of Defective Endoreplication During Developmentmentioning

confidence: 99%

Endoreplication and polyploidy: insights into development and disease

2013

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SummaryPolyploid cells have genomes that contain multiples of the typical diploid chromosome number and are found in many different organisms. Studies in a variety of animal and plant developmental systems have revealed evolutionarily conserved mechanisms that control the generation of polyploidy and have recently begun to provide clues to its physiological function. These studies demonstrate that cellular polyploidy plays important roles during normal development and also contributes to human disease, particularly cancer.Key words: Cancer, Endocycle, Endomitosis, Endoreplication, Genome instability IntroductionPolyploid cells, which contain multiples of the diploid genome equivalent, have been studied for many years, nearly as long as chromosomes themselves have been studied. Now, over a century after the discovery of polyploidy, we know much about the molecular mechanisms that generate cellular polyploidy, but comparably little regarding the physiological function of the polyploid state. This discrepancy exists despite the frequent occurrence of polyploid cells in most multicellular organisms, as well as in human cancers. An important aspect of deciphering the roles for polyploidy lies in understanding the regulation of endoreplication, a cell cycle variation that generates a polyploid genome by repeated rounds of DNA replication in the absence of cell division. Recent advances show that, although some differences exist in the diverse endoreplication programs found from protists to humans, core principles can be applied. New work in genetic model organisms has identified cases in which programmed endoreplication plays key roles in development. Furthermore, recent evidence indicates that endoreplication can confer genome instability, a major cancer-enabling property. In this Primer (see Box), we review such recent discoveries, focusing on work carried out in the past 3 years, and refer the reader to other comprehensive reviews on this topic Lee et al., 2009). From these new insights emerge unifying themes regarding endoreplication that hold promise of elucidating the advantages, as well as the potential disadvantages, of polyploidy. Endoreplication and developmentEndoreplication is typically studied in the context of endopolyploidy, which refers to the presence of polyploid cells in an otherwise diploid organism. Diverse levels of polyploidy occur throughout nature (Table 1). Although polyploidy is well appreciated in plants , many different animal tissues, including the skin, gut, placenta, liver, brain and blood have polyploid cells (Table 1) (Laird et al., 1980;Corash et al., 1989;Fox et al., 2010; Hedgecock and White, 1985;Melaragno et al., 1993;Sherman, 1972;Unhavaithaya and Orr-Weaver, 2012;Zanet et al., 2010). Interestingly, endoreplication is not limited to multi-cellular organisms, with examples described in ciliated protozoa (Yin et al., 2010) and even bacteria (Mendell et al., 2008).Two primary forms of endoreplication have been described: endocycling and endomitosis (Fig. 1). Endocycles are compos...

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“…1A). Since the size of Drosophila larval muscles correlates with their number of nuclei (Demontis and Perrimon, 2009), we counted the number of nuclei in the DA3 muscle. Fewer nuclei were present in T2 and T3 (six on average) than in A1-A7 (eight on average) (Fig.…”

Section: Segment-specific Properties Of the Da3 Musclementioning

confidence: 99%

Multi-step control of muscle diversity by Hox proteins in the Drosophila embryo

et al. 2010

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SUMMARYHox transcription factors control many aspects of animal morphogenetic diversity. The segmental pattern of Drosophila larval muscles shows stereotyped variations along the anteroposterior body axis. Each muscle is seeded by a founder cell and the properties specific to each muscle reflect the expression by each founder cell of a specific combination of 'identity' transcription factors. Founder cells originate from asymmetric division of progenitor cells specified at fixed positions. Using the dorsal DA3 muscle lineage as a paradigm, we show here that Hox proteins play a decisive role in establishing the pattern of Drosophila muscles by controlling the expression of identity transcription factors, such as Nautilus and Collier (Col), at the progenitor stage. Highresolution analysis, using newly designed intron-containing reporter genes to detect primary transcripts, shows that the progenitor stage is the key step at which segment-specific information carried by Hox proteins is superimposed on intrasegmental positional information. Differential control of col transcription by the Antennapedia and Ultrabithorax/Abdominal-A paralogs is mediated by separate cis-regulatory modules (CRMs). Hox proteins also control the segment-specific number of myoblasts allocated to the DA3 muscle. We conclude that Hox proteins both regulate and contribute to the combinatorial code of transcription factors that specify muscle identity and act at several steps during the muscle-specification process to generate muscle diversity.

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Integration of Insulin receptor/Foxo signaling and dMyc activity during muscle growth regulates body size inDrosophila

Cited by 173 publications

References 85 publications

Life history evolution and cellular mechanisms associated with increased size in high‐altitude Drosophila

Life history evolution and cellular mechanisms associated with increased size in high‐altitude Drosophila

Endoreplication and polyploidy: insights into development and disease

Multi-step control of muscle diversity by Hox proteins in the Drosophila embryo

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