Vertebrate diapause preserves organisms long term through Polycomb complex members

Hu, Chi-Kuo; Wang, Wei; Brind’Amour, Julie; Singh, Param Priya; Reeves, G. Adam; Lorincz, Matthew C.; Alvarado, Alejandro Sánchez; Brunet, Anne

doi:10.1126/science.aaw2601

Cited by 87 publications

(76 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several laboratories are currently investigating the age-related phenotypes of genetically modified N. furzeri lines. Specific knock-out lines that have been generated in this species are Tert −/− [ 43 ] and Cbx7 −/− [ 44 ]. In the first case, the transgenic line was produced as a proof of concept of the CRISPR/Cas9-based genome editing approach; the gene was chosen to gain insights into the role of telomerase during aging (see also [ 44 ]).…”

Section: Major Interests and Research Questionsmentioning

confidence: 99%

“…Specific knock-out lines that have been generated in this species are Tert −/− [ 43 ] and Cbx7 −/− [ 44 ]. In the first case, the transgenic line was produced as a proof of concept of the CRISPR/Cas9-based genome editing approach; the gene was chosen to gain insights into the role of telomerase during aging (see also [ 44 ]). The second transgenic line was specifically created to investigate the role of Polycomb genes in diapause regulation [ 44 ].…”

Section: Major Interests and Research Questionsmentioning

confidence: 99%

“…3 a) [ 53 ]. Very recently, a role for Polycomb in the regulation of diapause was revealed [ 44 ]. Several laboratories are currently investigating killifish embryology and the molecular control of diapause.…”

Section: Major Interests and Research Questionsmentioning

confidence: 99%

See 2 more Smart Citations

Nothobranchius annual killifishes

Tozzini

Cellerino

2020

EvoDevo

View full text Add to dashboard Cite

Annual fishes of the genus Nothobranchius inhabit ephemeral habitats in Eastern and Southeastern Africa. Their life cycle is characterized by very rapid maturation, a posthatch lifespan of a few weeks to months and embryonic diapause to survive the dry season. The species N. furzeri holds the record of the fastest-maturing vertebrate and of the vertebrate with the shortest captive lifespan and is emerging as model organism in biomedical research, evolutionary biology, and developmental biology. Extensive characterization of age-related phenotypes in the laboratory and of ecology, distribution, and demography in the wild are available. Species/populations from habitats differing in precipitation intensity show parallel evolution of lifespan and age-related traits that conform to the classical theories on aging. Genome sequencing and the establishment of CRISPR/Cas9 techniques made this species particularly attractive to investigate the effects genetic and non-genetic intervention on lifespan and aging-related phenotypes. At the same time, annual fishes are a very interesting subject for comparative approaches, including genomics, transcriptomics, and proteomics. The N. furzeri community is highly diverse and rapidly expanding and organizes a biannual meeting.

show abstract

Section: Major Interests and Research Questionsmentioning

confidence: 99%

Section: Major Interests and Research Questionsmentioning

confidence: 99%

See 1 more Smart Citation

Nothobranchius annual killifishes

Tozzini

Cellerino

2020

EvoDevo

View full text Add to dashboard Cite

show abstract

“…N. furzeri was demonstrated to be an invaluable tool for studies in disparate branches of investigation such as evolutionary genomics (Reichwald et al, 2015;Valenzano et al, 2015;Sahm et al, 2017;Cui et al, 2020), regenerative medicine (Wendler et al, 2015), developmental biology (Dolfi et al, 2019;Hu et al, 2020), pharmacology (Valenzano et al, 2006;Baumgart et al, 2016) and ecotoxicology (Philippe et al, 2018). It was also shown that N. furzeri presents spontaneous age-dependent gliosis (Tozzini et al, 2012), neuronal protein aggregation and loss of stoichiometry of protein complexes in the brain that is triggered by early impairment of proteasome activity (Kelmer Sacramento et al, 2020) with selective agedependent degeneration of dopaminergic and noradrenergic neurons in the midbrain (Matsui et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

New lessons on TDP-43 from the killifishN. furzeri

Louka

Bagnoli

Rupert

et al. 2021

Preprint

View full text Add to dashboard Cite

Frontotemporal dementia and amyotrophic lateral sclerosis are fatal and incurable neurodegenerative diseases linked to the pathological aggregation of the TDP-43 protein. This is an essential DNA/RNA binding protein involved in transcription regulation, pre-RNA processing and RNA transport. Having suitable animal models to study the mechanisms of TDP-43 aggregation is crucial to develop treatments against disease. We have previously demonstrated that the killifish Nothobranchius furzeri offers the unique advantage as a model system that it is an organism with compressed lifespan and a conserved ageing phenotype that develops within months, making this organism the available shortest-lived vertebrate with a clear ageing phenotype. Here, we show that the two paralogs of TDP-43 from the killifish N. furzeri share high sequence homology with the human protein and recapitulate its cellular and biophysical behaviour. We prove that, during ageing, N. furzeri TDP-43 spontaneously forms insoluble intracellular TDP-43 aggregates that have amyloid characteristics and colocalize with the stress granule core protein G3BP. Our results propose this organism as a valuable model of TDP-43-related pathologies and show that even minute differences between the human and N. furzeri proteins may help to shed new light onto the role of TDP-43 in RNA recognition and granule formation.

show abstract

“…S1A) hatch in the absence of food ( 31 ), and expression of operons increases markedly during recovery from the L1 arrest ( 30 ). Vertebrate diapause was also recently shown to help organisms to survive long periods of time in extreme environments without trade-off for subsequent growth and fertility ( 32 ).…”

Section: Introductionmentioning

confidence: 99%

RNA polymerase II CTD S2P is dispensable for embryogenesis but mediates exit from developmental diapause in C. elegans

et al. 2020

View full text Add to dashboard Cite

Serine 2 phosphorylation (S2P) within the CTD of RNA polymerase II is considered a Cdk9/Cdk12-dependent mark required for 3′-end processing. However, the relevance of CTD S2P in metazoan development is unknown. We show that cdk-12 lesions or a full-length CTD S2A substitution results in an identical phenotype in Caenorhabditis elegans. Embryogenesis occurs in the complete absence of S2P, but the hatched larvae arrest development, mimicking the diapause induced when hatching occurs in the absence of food. Genome-wide analyses indicate that when CTD S2P is inhibited, only a subset of growth-related genes is not properly expressed. These genes correspond to SL2 trans-spliced mRNAs located in position 2 and over within operons. We show that CDK-12 is required for maximal occupancy of cleavage stimulatory factor necessary for SL2 trans-splicing. We propose that CTD S2P functions as a gene-specific signaling mark ensuring the nutritional control of the C. elegans developmental program.

show abstract

Vertebrate diapause preserves organisms long term through Polycomb complex members

Cited by 87 publications

References 47 publications

Nothobranchius annual killifishes

Nothobranchius annual killifishes

New lessons on TDP-43 from the killifishN. furzeri

RNA polymerase II CTD S2P is dispensable for embryogenesis but mediates exit from developmental diapause in C. elegans

Contact Info

Product

Resources

About