Polyploidy in the adult Drosophila brain

Nandakumar, Shyama; Grushko, Olga; Buttitta, Laura

doi:10.7554/elife.54385

Cited by 59 publications

(50 citation statements)

References 92 publications

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“…Our recent work has shown that neurons and glia become polyploid in the fly brain, specifically in the adult ( Nandakumar et al, 2020 ). Our study found that the optic lobes show higher levels of polyploidy than the central brain and the ventral nerve cord.…”

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

confidence: 99%

“…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%

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

Nandakumar

Rozich

Buttitta

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.

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

confidence: 99%

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

Nandakumar

Rozich

Buttitta

2021

Front. Cell Dev. Biol.

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“…For example, we describe variation amongst three WT Drosophila strains in the level of accumulating eccDNAs containing TE sequences (Fig. 5), while others have shown increased in polyploidy in adult Drosophila brains [110] as well as somatic genome instability in regions of the Drosophila genome [111] that might contribute to changes at the level of TE consensus sequence coverages (Fig. S3B).…”

Section: Discussionmentioning

confidence: 94%

Transposable element landscape changes are buffered by RNA silencing in agingDrosophila

Yang

Srivastav

Rahman

et al. 2021

Preprint

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Genetic mechanisms that repress transposable elements (TEs) in young animals decline during aging, as reflected by increased TE expression in aged animals. Does increased TE expression during aging lead to more genomic TE copies in older animals? To answer this question, we quantified TE Landscapes (TLs) via whole genome sequencing of young and aged Drosophila strains of wild-type and mutant backgrounds. We quantified TLs in whole flies and dissected brains and validated the feasibility of our approach in detecting new TE insertions in aging Drosophila genomes when natural defenses like RNA interference (RNAi) pathways are compromised. By also incorporating droplet digital PCR to validate genomic TE loads, we confirm TL changes can occur in a single lifespan of Drosophila when TEs are not suppressed. We also describe improved sequencing methods to quantify extra-chromosomal DNA circles (eccDNAs) in Drosophila as an additional source of TE copies that accumulate during aging. Lastly, to combat the natural progression of aging-associated TE expression, we show that knocking down PAF1, a conserved transcription elongation factor that antagonizes RNAi pathways, may bolster suppression of TEs during aging and extend lifespan. Our study suggests that RNAi mechanisms generally mitigate genomic TL expansion despite the increase in TE transcripts during aging.

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“…Together, these findings confirmed that there are cells in S phase in the adult brain (Figure 2b). However, S-phase markers can also reveal polyploid cells, present in the adult brain [38].…”

Section: There Are Proliferating Cells In the Adult Drosophila Brainmentioning

confidence: 99%

“…[2,3,27] Polyploidy in the adult brain. [38] Inference of mitosis from MARCM clones. Clones induced in the adult brain generated both glial and neuronal progeny cells.…”

Section: Cell Proliferationmentioning

confidence: 99%

Adult Neurogenesis in the Drosophila Brain: The Evidence and the Void

Hidalgo

2020

IJMS

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Establishing the existence and extent of neurogenesis in the adult brain throughout the animals including humans, would transform our understanding of how the brain works, and how to tackle brain damage and disease. Obtaining convincing, indisputable experimental evidence has generally been challenging. Here, we revise the state of this question in the fruit-fly Drosophila. The developmental neuroblasts that make the central nervous system and brain are eliminated, either through apoptosis or cell cycle exit, before the adult fly ecloses. Despite this, there is growing evidence that cell proliferation can take place in the adult brain. This occurs preferentially at, but not restricted to, a critical period. Adult proliferating cells can give rise to both glial cells and neurons. Neuronal activity, injury and genetic manipulation in the adult can increase the incidence of both gliogenesis and neurogenesis, and cell number. Most likely, adult glio- and neuro-genesis promote structural brain plasticity and homeostasis. However, a definitive visualisation of mitosis in the adult brain is still lacking, and the elusive adult progenitor cells are yet to be identified. Resolving these voids is important for the fundamental understanding of any brain. Given its powerful genetics, Drosophila can expedite discovery into mammalian adult neurogenesis in the healthy and diseased brain.

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Polyploidy in the adult Drosophila brain

Cited by 59 publications

References 92 publications

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

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

Transposable element landscape changes are buffered by RNA silencing in agingDrosophila

Adult Neurogenesis in the Drosophila Brain: The Evidence and the Void

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