Endoreplication: A Molecular Trick during Animal Neuron Evolution

Mandrioli, Mauro; Mola, Lucrezia; Cuoghi, Barbara; Sonetti, Dario

doi:10.1086/652341

Cited by 11 publications

(12 citation statements)

References 40 publications

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“…Thus we wanted to test whether the nuclear size increase is due to DNA-endoreplication, as proposed for giant neurons in mollusks [27], [76]. Endoreplication entails DNA synthesis in absence of cell division and leads to increased cell size and either polyploidy or replication of some genomic regions, polygeny [77]. Increases in DNA ploidy can be induced by growth and IIS/TOR signaling in endoreplicating tissues [47], [78].…”

Section: Resultsmentioning

confidence: 99%

Insulin/IGF-Regulated Size Scaling of Neuroendocrine Cells Expressing the bHLH Transcription Factor Dimmed in Drosophila

2013

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Neurons and other cells display a large variation in size in an organism. Thus, a fundamental question is how growth of individual cells and their organelles is regulated. Is size scaling of individual neurons regulated post-mitotically, independent of growth of the entire CNS? Although the role of insulin/IGF-signaling (IIS) in growth of tissues and whole organisms is well established, it is not known whether it regulates the size of individual neurons. We therefore studied the role of IIS in the size scaling of neurons in the Drosophila CNS. By targeted genetic manipulations of insulin receptor (dInR) expression in a variety of neuron types we demonstrate that the cell size is affected only in neuroendocrine cells specified by the bHLH transcription factor DIMMED (DIMM). Several populations of DIMM-positive neurons tested displayed enlarged cell bodies after overexpression of the dInR, as well as PI3 kinase and Akt1 (protein kinase B), whereas DIMM-negative neurons did not respond to dInR manipulations. Knockdown of these components produce the opposite phenotype. Increased growth can also be induced by targeted overexpression of nutrient-dependent TOR (target of rapamycin) signaling components, such as Rheb (small GTPase), TOR and S6K (S6 kinase). After Dimm-knockdown in neuroendocrine cells manipulations of dInR expression have significantly less effects on cell size. We also show that dInR expression in neuroendocrine cells can be altered by up or down-regulation of Dimm. This novel dInR-regulated size scaling is seen during postembryonic development, continues in the aging adult and is diet dependent. The increase in cell size includes cell body, axon terminations, nucleus and Golgi apparatus. We suggest that the dInR-mediated scaling of neuroendocrine cells is part of a plasticity that adapts the secretory capacity to changing physiological conditions and nutrient-dependent organismal growth.

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Section: Resultsmentioning

confidence: 99%

Insulin/IGF-Regulated Size Scaling of Neuroendocrine Cells Expressing the bHLH Transcription Factor Dimmed in Drosophila

2013

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“…However, some other adult human tissues undergo endocycles during differentiation [35], [36], [37], [62], [63]. Endoreplication might have been disregarded in human epidermis because of the technical difficulties to visualise binucleate cells on skin sections or to isolate late differentiating cells from epidermis and because most polyploid keratinocytes might have a single nucleus.…”

Section: Discussionmentioning

confidence: 99%

A Mitosis Block Links Active Cell Cycle with Human Epidermal Differentiation and Results in Endoreplication

et al. 2010

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How human self-renewal tissues co-ordinate proliferation with differentiation is unclear. Human epidermis undergoes continuous cell growth and differentiation and is permanently exposed to mutagenic hazard. Keratinocytes are thought to arrest cell growth and cell cycle prior to terminal differentiation. However, a growing body of evidence does not satisfy this model. For instance, it does not explain how skin maintains tissue structure in hyperproliferative benign lesions. We have developed and applied novel cell cycle techniques to human skin in situ and determined the dynamics of key cell cycle regulators of DNA replication or mitosis, such as cyclins E, A and B, or members of the anaphase promoting complex pathway: cdc14A, Ndc80/Hec1 and Aurora kinase B. The results show that actively cycling keratinocytes initiate terminal differentiation, arrest in mitosis, continue DNA replication in a special G2/M state, and become polyploid by mitotic slippage. They unambiguously demonstrate that cell cycle progression coexists with terminal differentiation, thus explaining how differentiating cells increase in size. Epidermal differentiating cells arrest in mitosis and a genotoxic-induced mitosis block rapidly pushes epidermal basal cells into differentiation and polyploidy. These observations unravel a novel mitosis-differentiation link that provides new insight into skin homeostasis and cancer. It might constitute a self-defence mechanism against oncogenic alterations such as Myc deregulation.

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“…hymenopterans), endopolyploid levels can reach 512C across tissues such as Malpighian tubules, small intestine, and thoracic gland , and salivary glands routinely achieve endopolyploid levels of 1024C or more (Nagl, 1978). The neurons of molluscs feature remarkable ploidy variation, from a modest 32C in the land snail Triodopsis divesta to an astounding 200000C in the gigantic neurons of the sea hare Aplysia californica (Lasek & Dower, 1971;Mandrioli et al, 2010). The highest endopolyploid level that has been recorded in any animal is >500000C, reported from the silk-producing glands of the silk moth Bombyx mori (Perdrix-Gillot, 1979;Gregory & Hebert, 1999).…”

Section: Where Does Endopolyploidy Occur?mentioning

confidence: 99%

Endopolyploidy as a potential driver of animal ecology and evolution

et al. 2015

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Endopolyploidy - the existence of higher-ploidy cells within organisms that are otherwise of a lower ploidy level (generally diploid) - was discovered decades ago, but remains poorly studied relative to other genomic phenomena, especially in animals. Our synthetic review suggests that endopolyploidy is more common in animals than often recognized and probably influences a number of fitness-related and ecologically important traits. In particular, we argue that endopolyploidy is likely to play a central role in key traits such as gene expression, body and cell size, and growth rate, and in a variety of cell types, including those responsible for tissue regeneration, nutrient storage, and inducible anti-predator defences. We also summarize evidence for intraspecific genetic variation in endopolyploid levels and make the case that the existence of this variation suggests that endopolyploid levels are likely to be heritable and thus a potential target for natural selection. We then discuss why, in light of evident benefits of endopolyploidy, animals remain primarily diploid. We conclude by highlighting key areas for future research such as comprehensive evaluation of the heritability of endopolyploidy and the adaptive scope of endopolyploid-related traits, the extent to which endopolyploid induction incurs costs, and characterization of the relationships between environmental variability and endopolyploid levels.

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Endoreplication: A Molecular Trick during Animal Neuron Evolution

Cited by 11 publications

References 40 publications

Insulin/IGF-Regulated Size Scaling of Neuroendocrine Cells Expressing the bHLH Transcription Factor Dimmed in Drosophila

Insulin/IGF-Regulated Size Scaling of Neuroendocrine Cells Expressing the bHLH Transcription Factor Dimmed in Drosophila

A Mitosis Block Links Active Cell Cycle with Human Epidermal Differentiation and Results in Endoreplication

Endopolyploidy as a potential driver of animal ecology and evolution

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