Notch-dependent DNAcis-regulatory elements and their dose-dependent control ofC. elegansstem cell self-renewal DOI Creative Commons
Tina R. Lynch, Mingyu Xue,

Cazza W. Czerniak

и другие.

Development, Год журнала: 2022, Номер 149(7)

Опубликована: Апрель 1, 2022

ABSTRACT A long-standing biological question is how DNA cis-regulatory elements shape transcriptional patterns during metazoan development. Reporter constructs, cell culture assays and computational modeling have made major contributions to answering this question, but analysis of in their natural context an important complement. Here, we mutate Notch-dependent LAG-1 binding sites (LBSs) the endogenous Caenorhabditis elegans sygl-1 gene, which encodes a key stem regulator, analyze consequences on expression (nascent transcripts, mRNA, protein) maintenance. Mutation one LBS three-element cluster approximately halved both pool size, whereas mutation two LBSs essentially abolished them. Heterozygous mutant clusters provided intermediate values. Our results lead conclusions. First, number configuration impact activity: act additively trans synergistically cis. Second, SYGL-1 gradient promotes self-renewal above its functional threshold triggers differentiation below threshold. approach coupling CRISPR/Cas9 mutations with effects molecular readouts establishes powerful model for vivo analyses elements.

Язык: Английский

Analysis of the C. elegans Germline Stem Cell Pool DOI

Sarah L. Crittenden,

Hannah S. Seidel, Judith Kimble

и другие.

Methods in molecular biology, Год журнала: 2023, Номер unknown, С. 1 - 36

Опубликована: Янв. 1, 2023

Язык: Английский

Процитировано

7
Mechanochemical feedback loops in contact-dependent fate patterning DOI Creative Commons

Tim Dullweber,

Anna Erzberger

Current Opinion in Systems Biology, Год журнала: 2023, Номер 32-33, С. 100445 - 100445

Опубликована: Фев. 6, 2023

To reliably form and maintain structures with specific functions, many multicellular systems evolved to leverage the interplay between biochemical signaling, mechanics, morphology. We review mechanochemical feedback loops in cases where cell–cell contact-based Notch signaling drives fate decisions, corresponding differentiation process leads contact remodeling. compare different mechanisms for initial symmetry breaking subsequent pattern refinement, as well discuss how patterning outcomes depend on relationship mechanical timescales. conclude an overview of new approaches, including study synthetic circuits, give outlook future experimental theoretical developments toward dissecting harnessing feedback.

Язык: Английский

Процитировано

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

Tyler Jung

и другие.

Biology Open, Год журнала: 2023, Номер 13(1)

Опубликована: Дек. 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.

Язык: Английский

Процитировано

5
Notch-dependent DNAcis-regulatory elements and their dose-dependent control ofC. elegansstem cell self-renewal DOI Creative Commons
Tina R. Lynch, Mingyu Xue,

Cazza W. Czerniak

и другие.

Development, Год журнала: 2022, Номер 149(7)

Опубликована: Апрель 1, 2022

ABSTRACT A long-standing biological question is how DNA cis-regulatory elements shape transcriptional patterns during metazoan development. Reporter constructs, cell culture assays and computational modeling have made major contributions to answering this question, but analysis of in their natural context an important complement. Here, we mutate Notch-dependent LAG-1 binding sites (LBSs) the endogenous Caenorhabditis elegans sygl-1 gene, which encodes a key stem regulator, analyze consequences on expression (nascent transcripts, mRNA, protein) maintenance. Mutation one LBS three-element cluster approximately halved both pool size, whereas mutation two LBSs essentially abolished them. Heterozygous mutant clusters provided intermediate values. Our results lead conclusions. First, number configuration impact activity: act additively trans synergistically cis. Second, SYGL-1 gradient promotes self-renewal above its functional threshold triggers differentiation below threshold. approach coupling CRISPR/Cas9 mutations with effects molecular readouts establishes powerful model for vivo analyses elements.

Язык: Английский

Процитировано

6