Communal living: the role of polyploidy and syncytia in tissue biology

Peterson, Nora G.; Fox, Donald T.

doi:10.1007/s10577-021-09664-3

Cited by 32 publications

(22 citation statements)

References 171 publications

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“…3a ). Fancd2 plays a major role in S-phase and it is possible that cells that frequently enter S-phase (endocycling cells) would have increased Fancd2 dependency ( Moldovan and D’Andrea 2009 ; Rodríguez and D’Andrea 2017 ; Niraj et al 2019 ; Peterson and Fox 2021 ). Additionally, neural brain progenitors also contain pan-nuclear GFP-Fancd2 WT expression ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Conserved function ofDrosophilaFancd2 monoubiquitination in response to double-strand DNA breaks

Clay

Jezuit

Montague

et al. 2022

G3 Genes|Genomes|Genetics

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Fanconi anemia genes play key roles in metazoan DNA damage responses, and human FA mutations cause numerous disease phenotypes. In human cells, activating monoubiquitination of the Fanconi anemia protein Fancd2 occurs following diverse DNA damage stimuli. Monoubiquitinated Fancd2 forms nuclear foci to recruit additional repair factors. Fancd2 animal models to date have focused on molecular nulls or whole gene knockdown, leaving the specific in vivo role of monoubiquitination unclear. Using a point mutant in a conserved residue, we recently linked Drosophila Fancd2 monoubiquitination to a mitosis-specific DNA double-strand break response. In this context, we used CRISPR/Cas9 to generate the first animal model of an endogenous mutation in the conserved monoubiquitination site (fancd2K595R). Here, we expand upon our characterization of fancd2K595R. We also introduce and characterize additional Drosophila tools to study fancd2, including new mutant alleles and GFP-tagged rescue transgenes. Using these new reagents, we show the impact of Drosophila Fancd2 on organismal and cell viability, as well as on repair protein localization, in the presence or absence of double-strand breaks. These findings expand our understanding of Fanconi anemia gene function in vivo and provide useful reagents for DNA repair research.

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Section: Resultsmentioning

confidence: 99%

Conserved function ofDrosophilaFancd2 monoubiquitination in response to double-strand DNA breaks

Clay

Jezuit

Montague

et al. 2022

G3 Genes|Genomes|Genetics

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“…Polyploidy has been associated with large cells or cells that need to be metabolically active, as a way to scale their power of biosynthesis to their cellular functions 43,50,82 . For example, the megakaryocytes of the bone marrow, which are required to generate large quantities of mRNA and protein for producing platelets, undergo polyploidization.…”

Section: Discussionmentioning

confidence: 99%

An interplay between cellular growth and atypical fusion defines morphogenesis of a modular glial niche in Drosophila

et al. 2022

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Neural stem cells (NSCs) live in an intricate cellular microenvironment supporting their activity, the niche. Whilst shape and function are inseparable, the morphogenetic aspects of niche development are poorly understood. Here, we use the formation of a glial niche to investigate acquisition of architectural complexity. Cortex glia (CG) in Drosophila regulate neurogenesis and build a reticular structure around NSCs. We first show that individual CG cells grow tremendously to ensheath several NSC lineages, employing elaborate proliferative mechanisms which convert these cells into syncytia rich in cytoplasmic bridges. CG syncytia further undergo homotypic cell–cell fusion, using defined cell surface receptors and actin regulators. Cellular exchange is however dynamic in space and time. This atypical cell fusion remodels cellular borders, restructuring the CG syncytia. Ultimately, combined growth and fusion builds the multi-level architecture of the niche, and creates a modular, spatial partition of the NSC population. Our findings provide insights into how a niche forms and organises while developing intimate contacts with a stem cell population.

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“…However, the fact that CMs increase volume many times over with the same nuclear number questions that relationship. The process of bi-, multi-nucleation, and polyploidy is inhibitory to cell division in CMs [ 124 , 125 ], but what is the role of having multiple copies of DNA in one cell? Recent studies have provided evidence that the multiple copies of DNA may not all be performing the same function.…”

Section: Cardiomyocyte Neonatal Growthmentioning

confidence: 99%

Cardiomyocyte Proliferation from Fetal- to Adult- and from Normal- to Hypertrophy and Failing Hearts

Bishop

Zhang

2022

Biology

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The cardiomyocyte undergoes dramatic changes in structure, metabolism, and function from the early fetal stage of hyperplastic cell growth, through birth and the conversion to hypertrophic cell growth, continuing to the adult stage and responding to various forms of stress on the myocardium, often leading to myocardial failure. The fetal cell with incompletely formed sarcomeres and other cellular and extracellular components is actively undergoing mitosis, organelle dispersion, and formation of daughter cells. In the first few days of neonatal life, the heart is able to repair fully from injury, but not after conversion to hypertrophic growth. Structural and metabolic changes occur following conversion to hypertrophic growth which forms a barrier to further cardiomyocyte division, though interstitial components continue dividing to keep pace with cardiac growth. Both intra- and extracellular structural changes occur in the stressed myocardium which together with hemodynamic alterations lead to metabolic and functional alterations of myocardial failure. This review probes some of the questions regarding conditions that regulate normal and pathologic growth of the heart.

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Communal living: the role of polyploidy and syncytia in tissue biology

Cited by 32 publications

References 171 publications

Conserved function ofDrosophilaFancd2 monoubiquitination in response to double-strand DNA breaks

Conserved function ofDrosophilaFancd2 monoubiquitination in response to double-strand DNA breaks

An interplay between cellular growth and atypical fusion defines morphogenesis of a modular glial niche in Drosophila

Cardiomyocyte Proliferation from Fetal- to Adult- and from Normal- to Hypertrophy and Failing Hearts

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