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

John McCloskey,

Judith Kimble

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2020, Volume and Issue: unknown

Published: June 24, 2020

Abstract Genes encoding powerful developmental regulators are exquisitely controlled, often at multiple levels. Here, we use single molecule FISH (smFISH) to investigate nuclear active transcription sites (ATS) and cytoplasmic mRNAs of three key regulatory genes along the C. ele gans germline axis. The encode ERK/MAP kinase core components Notch-dependent complex. Using differentially-labeled probes spanning either a long first intron or downstream exons, identify two ATS classes that differ in transcriptional progression: iATS harbor partial nascent transcripts while cATS full-length transcripts. Remarkably, frequencies patterned axis gene-, stage- sex-specific manner. Moreover, regions with more frequent make fewer mRNAs, whereas those produce them. We propose regulated balance these has major impact on output during development.

Language: Английский

Biology of the Caenorhabditis elegans Germline Stem Cell System DOI Open Access
E. Jane Albert Hubbard, Tim Schedl

Genetics, Journal Year: 2019, Volume and Issue: 213(4), P. 1145 - 1188

Published: Dec. 1, 2019

Stem cell systems regulate tissue development and maintenance. The germline stem system is essential for animal reproduction, controlling both the timing number of progeny through its influence on gamete production. In this review, we first draw general comparisons to in other organisms, then present our current understanding

Language: Английский

Citations

119
Dynamics of Notch-Dependent Transcriptional Bursting in Its Native Context DOI Creative Commons
ChangHwan Lee, Heaji Shin, Judith Kimble

et al.

Developmental Cell, Journal Year: 2019, Volume and Issue: 50(4), P. 426 - 435.e4

Published: Aug. 1, 2019

Language: Английский

Citations

97
C. elegans germ granules require both assembly and localized regulators for mRNA repression DOI Creative Commons
Scott T. Aoki, Tina R. Lynch,

Sarah L. Crittenden

et al.

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Feb. 12, 2021

Abstract Cytoplasmic RNA–protein (RNP) granules have diverse biophysical properties, from liquid to solid, and play enigmatic roles in RNA metabolism. Nematode P are paradigmatic droplet central germ cell development. Here we analyze a key granule scaffolding protein, PGL-1, investigate the functional relationship between assembly function. Using protein–RNA tethering assay, find that reporter mRNA expression is repressed when recruited PGL-1. We determine crystal structure of PGL-1 N-terminal region 1.5 Å, discover its dimerization, identify residues at dimer interface. Mutations those interface prevent vivo, de-repress tethered mRNA, reduce fertility. Therefore, dimerization lies heart both Finally, granule-associated Argonaute WAGO-1 as crucial for repression mRNA. conclude function requires localized regulators.

Language: Английский

Citations

38
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
Non-autonomous regulation of germline stem cell proliferation by somatic MPK-1/MAPK activity in C. elegans DOI
Sarah L. Robinson,

Benjamin Dufour,

Pier-Olivier Martel

et al.

Cell Reports, Journal Year: 2021, Volume and Issue: 35(8), P. 109162 - 109162

Published: May 1, 2021

Language: Английский

Citations

23
Automated and customizable quantitative image analysis of wholeCaenorhabditis elegansgermlines DOI Creative Commons
Erik Toraason, Victoria L. Adler, Nicole Kurhanewicz

et al.

Genetics, Journal Year: 2021, Volume and Issue: 217(3)

Published: Jan. 23, 2021

Arranged in a spatial-temporal gradient for germ cell development, the adult germline of Caenorhabditis elegans is an excellent system understanding generation, differentiation, function, and maintenance cells. Imaging whole C. germlines along distal-proximal axis enables powerful cytological analyses nuclei as they progress from pre-meiotic tip through all stages meiotic prophase I. To enable high-content image analysis gonads, we developed custom algorithm pipelines to function with processing software that enables: (1) quantification features at single nucleus resolution immunofluorescence images; (2) assessment these individual based on their position within germline. We show capability our quantitative approach by analyzing multiple germlines. First, quantify double-strand DNA breaks (DSBs) per DNA-associated foci recombinase RAD-51 single-nucleus context progression. Second, DSBs are licensed crossover repair MSH-5 COSA-1 when associate synaptonemal complex during Finally, P-granule composition across colocalization PGL-1 ZNFX-1 foci. Our pipeline adaptable useful method researchers spanning fields using model system.

Language: Английский

Citations

18
Analysis of the C. elegans Germline Stem Cell Pool DOI

Sarah L. Crittenden,

Hannah S. Seidel, Judith Kimble

et al.

Methods in molecular biology, Journal Year: 2023, Volume and Issue: unknown, P. 1 - 36

Published: Jan. 1, 2023

Language: Английский

Citations

7
LST-1 is a bifunctional regulator that feeds back on Notch-dependent transcription to regulate C. elegans germline stem cells DOI Creative Commons
Ahlan Sabah Ferdous, Tina R. Lynch, Stephany J. Costa Dos Santos

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(39)

Published: Sept. 20, 2023

Notch signaling regulates stem cells across animal phylogeny. C. elegans activates transcription of two genes, lst-1 and sygl-1, that encode potent regulators germline cells. The LST-1 protein in distinct ways: It promotes self-renewal posttranscriptionally also restricts by a poorly understood mechanism. Its promoting activity resides its N-terminal region, while restricting C-terminal region requires the Zn finger. Here, we report limits down-regulating Notch-dependent transcription. We detect nucleus, addition to previously known cytoplasmic localization. lowers nascent transcript levels at both sygl-1 loci but not let-858, Notch-independent locus. key components activation complex, LAG-1 DNA binding intracellular domain (NICD). Genetically, an finger mutant increases strength gain- loss-of-function GLP-1/Notch receptor mutants. Biochemically, co-immunoprecipitates with from nematode extracts, suggesting direct effect. is thus bifunctional regulator coordinates posttranscriptional transcriptional mechanisms single protein. This bifunctionality relies on bipartite architecture bolstered generation isoforms, one specialized for downregulation. A conserved theme worms human coupling PUF-mediated RNA repression together feedback same

Language: Английский

Citations

7
Recent Advances in the Genetic, Anatomical, and Environmental Regulation of the C. elegans Germ Line Progenitor Zone DOI Creative Commons
Kacy L. Gordon

Journal of Developmental Biology, Journal Year: 2020, Volume and Issue: 8(3), P. 14 - 14

Published: July 22, 2020

The C. elegans germ line and its gonadal support cells are well studied from a developmental genetics standpoint have revealed many foundational principles of stem cell niche biology. Among these the observations that niche-like supports self-renewing population with multipotential, differentiating daughter cells. While genetic features distinguish stem-like their progeny been defined, mechanisms structure populations in yet to be explained. spatial restriction Notch activation has emerged as an important principle acting distal line. Synthesizing recent findings, I present model which adult hermaphrodite can recognized two distinct anatomical populations. This review describes progress made characterizing undifferentiated gonad anatomy, presents open questions field new directions for research pursue.

Language: Английский

Citations

13
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