A sensitized genetic screen to identify regulators ofC. elegansgermline stem cells DOI Creative Commons
Sarah L. Robinson, Aaron M. Kershner, Heaji Shin

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2021, Volume and Issue: unknown

Published: Oct. 5, 2021

Abstract Germline stem cells (GSCs) in Caenorhabditis elegans are maintained by GLP-1/Notch signaling from the niche and a downstream RNA regulatory network. Loss of GLP-1 receptor causes GSCs to precociously undergo meiotic differentiation, “Glp” phenotype, due failure self-renew. lst-1 sygl-1 functionally redundant direct targets whose gene products work with PUF binding proteins promote GSC self-renewal. Whereas single loss-of-function mutants fertile, double sterile Glp. We set out identify genes that function redundantly either or maintain GSCs. To this end, we conducted forward genetic screens for Glp backgrounds lacking functional copies . The generated nine glp-1 alleles, two one allele pole-1 , which encodes catalytic subunit DNA polymerase ε. Three alleles reside Ankyrin (ANK) repeats not previously mutated. have low penetrance is enhanced loss Thus, screen uncovered locus interacts genetically both useful mutations further studies regulation.

Language: Английский

The Rac pathway prevents cell fragmentation in a nonprotrusively migrating leader cell during C. elegans gonad organogenesis DOI
Noor Singh, Pu Zhang,

Karen Jian Li

et al.

Current Biology, Journal Year: 2024, Volume and Issue: 34(11), P. 2387 - 2402.e5

Published: May 21, 2024

Language: Английский

Citations

6
MIG-21 is a novel regulator of Wnt and Netrin signaling in gonad migration identified from published scRNA-seq data and functionally validated inC. elegans DOI Creative Commons
Xin Li, Kacy L. Gordon

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

Using a recently published scRNA-seq dataset of adult C. elegans hermaphrodites, we identified previously unknown regulator the germ line stem cell niche (the distal tip cell, or DTC). The gene mig-21 has highest "marker score"-yet no known role-in DTC. classical genetics techniques, RNAi knockdown, and live imaging, discovered that integrates information from Wnt Netrin pathways to guide anteroposterior dorsoventral DTC migration. Our study demonstrates utility datasets in revealing testable hypotheses about genetic networks were masked by redundancy traditional screening methods.

Language: Английский

Citations

0
Comprehensive comparative analysis of the effects of temperature on the Notch signaling responsein vivo DOI Creative Commons
Nimmy S. John,

Kin Tang,

Michelle A. Urman

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 19, 2025

Abstract Temperature is a critical factor that modulates cellular metabolism and stem cell regulation. Despite extensive studies, the influence of temperature on regulation via Notch signaling has been limited to studies relying involve indirect readouts activation. This study systematically analyzes effects transcriptional response at chromosomal, cellular, tissue levels. Using complementary direct readouts, we demonstrate activation remains largely unchanged across temperatures, suggesting presence temperature-compensatory mechanisms maintain robust activity however, increased with temperature, indicating elevated temperatures may enhance chromosomal level. These findings provide comprehensive framework for understanding offer new insights into in biology.

Language: Английский

Citations

0
Reproductive Toxicity of Furfural Acetone in Meloidogyne incognita and Caenorhabditis elegans DOI Creative Commons
Wanli Cheng, Xue Yang, Hua Xue

et al.

Cells, Journal Year: 2022, Volume and Issue: 11(3), P. 401 - 401

Published: Jan. 25, 2022

Furfural acetone (FAc) is a promising alternative to currently available nematicides, and it exhibits equivalent control efficiency on root-knot nematodes with avermectin in fields. However, its effect the reproduction of nematode poorly understood. In this study, natural metabolite FAc was found exhibit reproductive toxicity Meloidogyne incognita Caenorhabditis elegans. The number germ cells C. elegans observed decrease after exposure FAc, reduction 59.9% at dose 200 mg/L. various concentrations induced germ-cell apoptosis elegans, an increase over six-fold apoptotic These findings suggested that decreased brood size by inducing apoptosis. Moreover, FAc-induced suppressed mutation gene hus-1, clk-2, cep-1, egl-1, ced-3, ced-4, or ced-9. expression genes spo-11, egl-1 increased significantly treatment. Taken together, these results indicate might inflict DNA damage through protein SPO-11, activate CEP-1 EGL-1, induce core pathway cause apoptosis, resulting

Language: Английский

Citations

14
Higher-order epistasis shapes natural variation in germ stem cell niche activity DOI Creative Commons
Sarah R. Fausett,

Asma Sandjak,

Bénédicte Billard

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: May 17, 2023

Abstract To study how natural allelic variation explains quantitative developmental system variation, we characterized differences in germ stem cell niche activity, measured as progenitor zone (PZ) size, between two Caenorhabditis elegans isolates. Linkage mapping yielded candidate loci on chromosomes II and V, found that the isolate with a smaller PZ size harbours 148 bp promoter deletion Notch ligand, lag-2/Delta , central signal promoting fate. As predicted, introducing this into large resulted size. Unexpectedly, restoring deleted ancestral sequence did not increase—but instead further reduced—PZ These seemingly contradictory phenotypic effects are explained by epistatic interactions promoter, chromosome locus, additional background loci. results provide first insights genetic architecture regulating an animal system.

Language: Английский

Citations

8
Caenorhabditis elegans septins contribute to the development and structure of the oogenic germline DOI
Jenna A. Perry, Michael E. Werner, Larry Rivenbark

et al.

Cytoskeleton, Journal Year: 2023, Volume and Issue: 80(7-8), P. 215 - 227

Published: June 2, 2023

Oocytes must be exceptionally large cells in order to support embryonic development. Throughout animal phylogeny, a specialized cell called syncytium, wherein many nuclei share continuous cytoplasm, achieves oogenesis. The syncytial nature of germline architecture is key its function and depends on conserved components the cortical cytoskeleton. Septins form non-polar cytoskeletal polymers that associate with membranes. In nematode Caenorhabditis elegans, septins are highly enriched cortex generally required for fertility, but role poorly understood. We report C. elegans septins, UNC-59 UNC-61, important extension during development, maintenance architecture, production oocytes. While much our findings substantiate idea two act together, we also found evidence they have distinct functions. Loss UNC-61 perturbed while loss severely affected adult hermaphrodites. Consultation clustering results from large-scale high-throughput screen suggested involved germ proliferation and/or differentiation. sum, implicate component complex syncytium.

Language: Английский

Citations

5
Aging disrupts spatiotemporal regulation of germline stem cells and niche integrity DOI Creative Commons
Michelle A. Urman, Nimmy S. John,

Tyler Jung

et al.

Biology Open, Journal Year: 2023, Volume and Issue: 13(1)

Published: Dec. 29, 2023

ABSTRACT A major factor driving stem cell decline is niche aging, but its molecular mechanism remains elusive. We use the Caenorhabditis elegans distal tip (DTC), mesenchymal that employs Notch signaling to regulate germline cells (GSCs), as an in vivo aging model and delineate details of DTC/niche process. Here, we demonstrate a drastic decrease C. fecundity, which begins even early adulthood, mainly due age-induced disruption spatial regulation Notch-dependent transcription combined with moderate reduction at both tissue cellular levels. Consequently, Notch-responsive GSC pool shifts from end gonad more proximal region, disrupting distal-to-proximal polarity. find this shift dislocation nucleus, associated changes structure morphology DTC/niche. Our findings reveal critical link between physiological niche, their consequences regulation, functions.

Language: Английский

Citations

4
Higher-order epistasis shapes natural variation in germ stem cell niche activity DOI Creative Commons
Sarah R. Fausett,

Asma Sandjak,

Bénédicte Billard

et al.

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

Published: Nov. 4, 2022

Summary Natural quantitative variation in developmental processes must be driven by allelic variation. Yet, the genotype-phenotype relationships underlying system are understudied due to their inherent complexity. Taking advantage of simple Caenorhabditis elegans germline stem cell system, we characterized natural differences germ niche activity two distinct wild isolates—measured as progenitor zone (PZ) size. Through trait locus (QTL) analysis, detected multiple candidate causal loci, including large-effect QTL on chromosomes II and V. Resolving chromosome V QTL, show that isolate with a smaller PZ exhibits unique 148 bp deletion promoter region Notch ligand, lag-2 , central signal promoting fate proliferation. As predicted, introducing this into large resulted PZ. Unexpectedly, re-introducing deleted ancestral sequence further reduced Using replacement lines, these contradictory phenotypic effects epistatic interactions among promoter, additional loci genome. Although appeared explain activity, its across genetic backgrounds were unpredictable higher-order epistasis. Studying architecture systems without taking account may misleading, emphasizing need for better integration genetics.

Language: Английский

Citations

5
Simplified Quantification of Progenitor Zone Size, an Indicator of Germ Stem Cell Niche Activity, in the Nematode Caenorhabditis elegans DOI
Sarah R. Fausett,

Caroline A. Laury,

Rachel E. Magallon

et al.

Methods in molecular biology, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Language: Английский

Citations

0
Niche-adjacent Type IV collagen promotes GLP-1/Notch receptor activation in the C. elegans germline DOI Creative Commons
Patrick Narbonne, Pier-Olivier Martel,

Julia Degrémont

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: May 8, 2024

Abstract Basement membranes are thin and dense proteinaceous layers of specialized extracellular matrix that surround tissues to maintain their structure function1. With age, chronic inflammation typically stiffens this basement membrane in a phenomenon called fibrosis, the progression which is reflected by increasing levels membrane’s main component, type IV collagen (COL IV)2,3. Tissue fibrosis elevated Notch signaling two co-occurring hallmarks many inflammation-linked diseases, including cancer3-6. Many reasoned may be consequence signaling, belief has led targeting antifibrotic therapy attempts7,8,9. Yet, in vivo relationship between activity not been clearly defined. Here, we show EMB-9/COL accumulation adjacent C. elegans germline stem cell niche promotes GLP-1/Notch receptor activation germline cells. Increased therefore high COL contents. Moreover, find reducing leads generalized dramatic increase levels, thereby fibrosis. The comes along with inflammaging act as root cause for cancer promoting perhaps more widely, other ligand-receptor interactions.

Language: Английский

Citations

0