Cell cycle variants during Drosophila accessory gland development

Grushko

2020

eLife

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Long-lived cells such as terminally differentiated postmitotic neurons and glia must cope with the accumulation of damage over the course of an animal’s lifespan. How long-lived cells deal with ageing-related damage is poorly understood. Here we show that polyploid cells accumulate in the adult fly brain and that polyploidy protects against DNA damage-induced cell death. Multiple types of neurons and glia that are diploid at eclosion, become polyploid in the adult Drosophila brain. The optic lobes exhibit the highest levels of polyploidy, associated with an elevated DNA damage response in this brain region. Inducing oxidative stress or exogenous DNA damage leads to an earlier onset of polyploidy, and polyploid cells in the adult brain are more resistant to DNA damage-induced cell death than diploid cells. Our results suggest polyploidy may serve a protective role for neurons and glia in adult Drosophila melanogaster brains.

Section: Discussionmentioning

confidence: 99%

Polyploidy in the adult Drosophila brain

Grushko

2020

eLife

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“…Some SPGs in the fly blood brain barrier are known to become multinucleate by endomitosis ( Eliades et al, 2010 ; Unhavaithaya and Orr-Weaver, 2012 ; Von Stetina et al, 2018 ). Examples of endomitosis giving rise to binucleate cells are cardiomyocytes in mouse and human hearts, lactating mammary epithelial cells and the binucleate cells of the Drosophila accessory gland ( Stephen et al, 2009 ; Pandit et al, 2013 ; Paradis et al, 2014 ; Taniguchi et al, 2014 , 2018 ; Box et al, 2019 ).…”

Section: Are All Terminally Differentiated Neurons Permanently Diploid and In G0?mentioning

confidence: 99%

“…Other examples of endocycling in response to cell loss include the epicardium of the zebrafish heart ( Uroz et al, 2019 ). In Drosophila , the enterocytes of the intestinal epithelium, the follicle cells of the ovary and the main cells of the accessory gland can cope with induced cell death by engaging a compensatory cellular hypertrophy or endocycle program to maintain tissue size and homeostasis ( Tamori and Deng, 2013 ; Edgar et al, 2014 ; Shu et al, 2018 ; Øvrebø and Edgar, 2018 ; Box et al, 2019 ). In the fly optic lobe, where increase in polyploidy is accompanied by a steady loss of diploid cells, polyploidization may serve a compensatory role by enabling neurons to form more synaptic connections to compensate for cell loss to maintain visual acuity ( Nandakumar et al, 2020 ).…”

Section: Are All Terminally Differentiated Neurons Permanently Diploid and In G0?mentioning

confidence: 99%

Cell Cycle Re-entry in the Nervous System: From Polyploidy to Neurodegeneration

Rozich

2021

Front. Cell Dev. Biol.

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Terminally differentiated cells of the nervous system have long been considered to be in a stable non-cycling state and are often considered to be permanently in G0. Exit from the cell cycle during development is often coincident with the differentiation of neurons, and is critical for neuronal function. But what happens in long lived postmitotic tissues that accumulate cell damage or suffer cell loss during aging? In other contexts, cells that are normally non-dividing or postmitotic can or re-enter the cell cycle and begin replicating their DNA to facilitate cellular growth in response to cell loss. This leads to a state called polyploidy, where cells contain multiple copies of the genome. A growing body of literature from several vertebrate and invertebrate model organisms has shown that polyploidy in the nervous system may be more common than previously appreciated and occurs under normal physiological conditions. Moreover, it has been found that neuronal polyploidization can play a protective role when cells are challenged with DNA damage or oxidative stress. By contrast, work over the last two and a half decades has discovered a link between cell-cycle reentry in neurons and several neurodegenerative conditions. In this context, neuronal cell cycle re-entry is widely considered to be aberrant and deleterious to neuronal health. In this review, we highlight historical and emerging reports of polyploidy in the nervous systems of various vertebrate and invertebrate organisms. We discuss the potential functions of polyploidization in the nervous system, particularly in the context of long-lived cells and age-associated polyploidization. Finally, we attempt to reconcile the seemingly disparate associations of neuronal polyploidy with both neurodegeneration and neuroprotection.

“…Nurse cells in the egg chamber 81,82 , cells in the accessory gland 83,84 , salivary gland 85 and fat body 86 , on the other hand become polyploid to fulfill increased biosynthetic demands. In addition to an upregulation of DNA damage and cell cycle in the optic lobes, our RNAseq data suggests compromised metabolism with age in all parts of the brain.…”

Section: What Is the Function Of Polyploidisation In The Brain?mentioning

confidence: 99%

Polyploidy in the adultDrosophilabrain

Grushko

2019

Preprint

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Long-lived cells such as terminally differentiated postmitotic neurons and glia must cope with the accumulation of damage over the course of an animal's lifespan. How long-lived cells deal with ageing-related damage is poorly understood. Here we show that polyploid cells accumulate in the ageing adult fly brain and that polyploidy protects against DNA damage-induced cell death. Multiple types of neurons and glia that are diploid at eclosion, become polyploid with age in the adult Drosophila brain. The optic lobes exhibit the highest levels of polyploidy, associated with an elevated DNA damage response in this brain region with age. Inducing oxidative stress or exogenous DNA damage leads to an earlier onset of polyploidy, and polyploid cells in the adult brain are more resistant to DNA damage-induced cell death than diploid cells. Our results suggest polyploidy may serve a protective role for neurons and glia in ageing Drosophila melanogaster brains. for providing fly stocks, particularly the labs of Cheng-