Sensory neurons safeguard from mutational inheritance by controlling the CEP-1/p53-mediated DNA damage response in primordial germ cells DOI Creative Commons

Simon Uszkoreit,

David H. Meyer, Oded Rechavi

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: July 20, 2022

Abstract The genome integrity control in primordial germ cells (PGCs) is prerequisite for the inheritance of stable genomes. PGCs C. elegans are embedded a somatic niche that regulates its DNA damage response (DDR). Here, we show AMPK-like kinases KIN-29 and AAK-2 required arresting carrying persistent damage. We determined ASI neurons, which sense environmental conditions such as nutrient availability, secrete TGF-beta-like ligand DAF-7 recognized by DAF-1 receptor PGCs. ASI-dependent signaling induction CEP-1/p53 amid Using single worm whole sequencing, establish defective CEP-1/p53-regulated DDR ultimately results de novo germline mutations. Our indicate sensory neurons safeguard from mutations suggesting possibility perception environment could direct genetic inheritance. One sentence summary regulate CEP-1/p53-dependent via TGF-beta influence inherited mutational burden.

Language: Английский

Bidirectional transfer of a small membrane-impermeable molecule between the C. elegans intestine and germline DOI Creative Commons

Sarah Turmel-Couture,

Pier-Olivier Martel, Lucie Beaulieu

et al.

Journal of Biological Chemistry, Journal Year: 2024, Volume and Issue: 300(12), P. 107963 - 107963

Published: Nov. 5, 2024

Language: Английский

Citations

0
A non-canonical role of somatic Cyclin D/CYD-1 in oogenesis and in maintenance of reproductive fidelity, dependent on the FOXO/DAF-16 activation state DOI Creative Commons

Umanshi Rautela,

Gautam Chandra Sarkar, Ayushi Chaudhary

et al.

PLoS Genetics, Journal Year: 2024, Volume and Issue: 20(11), P. e1011453 - e1011453

Published: Nov. 15, 2024

For the optimal survival of a species, an organism coordinates its reproductive decisions with nutrient availability niche. Thus, nutrient-sensing pathways like insulin-IGF-1 signaling (IIS) play important role in modulating cell division, oogenesis, and aging. Lowering IIS leads to activation downstream FOXO transcription factor (TF) DAF-16 Caenorhabditis elegans which promotes oocyte quality delays However, less is known about how axis responds changes cycle proteins, particularly somatic tissues. Here, we show new aspect regulation germline by this axis. First, that canonical G1-S cyclin, Cyclin D/CYD-1, regulates fidelity from uterine tissue wild-type worms. Then, knocking down cyd-1 receptor mutant arrests oogenesis at pachytene stage meiosis-1 DAF-16-dependent manner. We observe activated deterioration gonadal tissues sheath cells, transcriptional de-regulation sperm-to-oocyte switch genes may be underlying reason for absence oogenesis. Deleting releases arrest restoration gonad but poor-quality oocytes are produced. Together, our study reveals unrecognized non-autonomous interaction D/CYD-1 FOXO/DAF-16 fidelity.

Language: Английский

Citations

0
Prenatal dexamethasone exposure reduces osteoprogenitor proliferation in mice via histone modifications at the Mkp-1 gene locus DOI Creative Commons

Yongheng Xie,

Jianwen Su,

Mankai Yang

et al.

Communications Biology, Journal Year: 2024, Volume and Issue: 7(1)

Published: Nov. 28, 2024

Prenatal dexamethasone exposure (PDE) has long-term consequences in bone development, though the underlying mechanisms remain unclear. Our results show that PDE offspring exhibit reduced mass, fewer osteoblasts and diminished osteoprogenitors proliferation. Further analyses increases MKP-1 expression, while decreasing H3 lysine 9 dimethylation (H3K9me2) 27 trimethylation (H3K27me3) at Mkp-1 gene locus. Mechanistically, suppresses proliferation by upregulating notably through inhibition of H3K9me2 H3K27me3 modifications, which promote demethylation transcriptional activation gene. Importantly, restoring histone methylation balance with PFI-90 or GSK-J4 treatment blocks inhibitory effects on MAPK signaling osteoprogenitors, mitigates detrimental impact osteoprogenitor development offspring. This study provides new insights into epigenetic mechanism disrupts programming fetal proliferation, ultimately impairing long growth modulates MKP-1/MAPK may account for effect prenatal consequent reduction mass mouse

Language: Английский

Citations

0
An RNAi screen of Rab GTPase genes in C. elegans reveals that somatic cells of the reproductive system depend on rab-1 for morphogenesis but not stem cell niche maintenance DOI Creative Commons

Kayt Scott,

Noor Singh, Kacy L. Gordon

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 6, 2024

Membrane trafficking is a crucial function of all cells and regulated at multiple levels from vesicle formation, packaging, localization to fusion, exocytosis, endocytosis. Rab GTPase proteins are core regulators eukaryotic membrane trafficking, but developmental roles specific GTPases less well characterized, potentially because their essentiality for basic cellular function.

Language: Английский

Citations

0
Two distinct mechanisms lead to either oocyte or spermatocyte decrease in C. elegans after whole developmental exposure to γ-rays DOI Creative Commons

Elizabeth Dufourcq‐Sekatcheff,

Christian Godon, Aymeric Bailly

et al.

PLoS ONE, Journal Year: 2023, Volume and Issue: 18(11), P. e0294766 - e0294766

Published: Nov. 27, 2023

Wildlife is subject to various sources of pollution, including ionizing radiation. Adverse effects can impact the survival, growth, or reproduction organisms, later affecting population dynamics. In invertebrates, reproduction, which directly impacts dynamics, has been found be most radiosensitive endpoint. Understanding underlying molecular pathways inducing this decrease help comprehend species-specific differences in radiosensitivity. From our previous studies, we that life stage dependent roundworm Caenorhabditis elegans, possibly resulting from an accumulation damages during germ cell development and gamete differentiation. To go further, used same experimental design assess more precisely determinants reproductive toxicity, primarily decreases number. As before, worms were chronically exposed 50 mGy·h-1 external gamma radiation throughout different developmental periods (namely embryogenesis, gametogenesis, full development). enable cross species extrapolation, conserved across invertebrates vertebrates analysed: apoptosis MAP kinase Ras/ERK (MPK-1), both involved stress responses. Our results showed these are life-stage dependent, upon chronic exposure IR development. The pathway was activated conditions pachytene region gonad where it regulates fate apoptosis, but not ovulation zone, controls oocyte maturation ovulation. Additionally, assessment proliferation via no effect. Finally, a functional analysis revealed while rate caused by DNA-damaged induced process does occur spermatocytes. Thus, sperm seems mediated another mechanism, probably speed needs further investigation better characterize sex-specific responses exposure. These main importance describe radio-induced reprotoxic contribute as weight evidence for AOP #396 "Deposition energy leads decline impaired meiosis".

Language: Английский

Citations

1
Two classes of active transcription sites and their roles in developmental regulation DOI Creative Commons
Sarah L. Robinson,

John McCloskey,

Judith Kimble

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2020, Volume and Issue: 117(43), P. 26812 - 26821

Published: Oct. 8, 2020

Significance Transcription occurs at chromosomal sites known as active transcription (ATS). We report that ATS can exist in two classes when assessed key regulatory genes their natural context: these “iATS” and “cATS” possess incomplete complete nascent transcripts, respectively. Frequencies of the are patterned within developing tissue a gene-, developmental stage-, sex-specific manner, revealing class regulation. Moreover, cATS frequency, not iATS corresponds to mRNA abundance, indicating regulation impacts gene expression. The signature—presence long first intron but lacking exons—suggests slowing or pausing transcriptional progression midway through gene. suggest pattern expression during development.

Language: Английский

Citations

1
Genetic and Chemical Controls of Sperm Fate and Spermatocyte Dedifferentiation in <em>Caenorhabditis elegans</em> DOI Open Access
Youngyong Park,

Matthew Gaddy,

Moonjung Hyun

et al.

Published: Dec. 21, 2022

Using the nematode C. elegans germline as a model system, we previously reported that PUF-8 (a PUF RNA-binding protein) and LIP-1 dual-specificity phosphatase) repress sperm fate at 20&deg;C dedifferentiation of spermatocytes into mitotic cells (termed "spermatocyte dedifferentiation") 25&deg;C. Thus, double mutants lacking both produce excess 20&deg;C, their return to mitotically dividing via 25&deg;C, resulting in tumors. To gain insight molecular competence for spermatocyte dedifferentiation, compared phenotypes three mutant strains &ndash; fem-3(q20gf), puf-8(q725; puf-8(q725); lip-1(zh15). Both fem-3(q20gf) produced like lip-1(zh15) mutants. Our results show was not observed mutants, but it more aggressive than These suggest MPK-1 (the ERK1/2 MAPK ortholog) activation by removing function absence promotes dedifferentiation. This idea confirmed using Resveratrol (RSV), potential activator human cells. Notably, significantly enhanced RSV treatment, its effect blocked mpk-1 RNAi. We, therefore, conclude are normally required inhibit tumorigenesis. Since these regulators broadly conserved, similar regulatory circuitry may control cellular tumorigenesis other organisms, including humans.

Language: Английский

Citations

1
long first intron enhances MPK-1B protein expression. DOI
Sarah L. Robinson, Judith Kimble

microPublication biology, Journal Year: 2021, Volume and Issue: 2021

Published: Jan. 14, 2021

Language: Английский

Citations

1
Two distinct mechanisms lead to either oocyte or spermatocyte decrease inC. elegansafter whole developmental exposure to γ-rays DOI Creative Commons

Elizabeth Dufourcq‐Sekatcheff,

Christian Godon, Aymeric Bailly

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: April 29, 2023

ABSTRACT Wildlife is subject to various sources of pollution, including ionizing radiation. Adverse effects can impact organisms’ survival, growth, or reproduction, later affecting population dynamics. In invertebrates, which directly impacts dynamics, has been found be the most radiosensitive endpoint. Understanding underlying molecular pathways inducing this reproduction decrease help comprehend species-specific differences in radiosensitivity. line with previous studies, we used a life stage dependent approach better understand determinants decrease, especially gamete hermaphrodite roundworm Caenorhabditis elegans . Worms were chronically exposed 50 mGy·h −1 external gamma radiations throughout different developmental periods (namely embryogenesis, gametogenesis, and full development). Conserved across invertebrates vertebrates involved processes stress response analyzed: apoptosis MAP kinase Ras/ERK (MPK-1). Our results showed that these are life-stage dependant, resulting from an accumulation damages upon chronic exposure IR whole development. The pathway was activated our conditions pachytene region gonad where it induces apoptotic pathway, but not ovulation zone, showing no incidence on oocyte maturation ovulation. Additionally, effect germ cell proliferation found, meaning probably process conditions. Finally, functional analysis revealed rate due DNA-damaged induced does occur spermatocytes. Thus, sperm seem mediated via another mechanism, cells speed needs further investigation characterize sex-specific responses exposure.

Language: Английский

Citations

0
Nutritional vitamin B12 regulates RAS/MAPK-mediated cell fate decisions through the one-carbon metabolism DOI Open Access

Ana Laranjeira,

Simon Berger, Tea Kohlbrenner

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 15, 2023

Abstract Vitamin B12 is an essential nutritional co-factor for the folate and methionine cycles, which together constitute one-carbon metabolism. Here, we show that dietary uptake of vitamin modulates cell fate decisions controlled by conserved RAS/MAPK signaling pathway in C. elegans . A bacterial diet rich increases vulval induction, germ apoptosis oocyte differentiation. These effects are mediated different metabolites a tissue-specific manner. enhances via choline/phosphatidylcholine metabolism induction down-regulating fat biosynthesis genes increasing H3K4 tri-methylation, results increased expression target genes. Furthermore, nucleotide tri-methylation positively regulate production. Using mammalian cells carrying activated KRAS BRAF alleles, on RAS/MAPK-regulated phenotype mammals. Our findings suggest B12-dependent limiting factor diverse RAS/MAPK-induced cellular responses.

Language: Английский

Citations

0