Comprehensive Research Report: lag-2 Gene in Caenorhabditis elegans Falcon Edison Scientific Literature 31 citations 3 artifacts 2026-09-30T05:31:19.450353
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Comprehensive Research Report: lag-2 Gene in Caenorhabditis elegans

Gene Identity and Overview

The lag-2 gene (UniProt: P45442) in Caenorhabditis elegans encodes LAG-2 (also known as LET-461), a transmembrane ligand belonging to the evolutionarily conserved Delta/Serrate/LAG-2 (DSL) family of Notch signaling proteins (luo2020positiveautoregulationof pages 1-4, holt2016characterisationofthe pages 124-128). The gene name derives from the characteristic "Lag" (lineage abnormal) phenotype observed in loss-of-function mutants, which fail to form the rectum and anus, resulting in larval arrest (holt2016characterisationofthe pages 124-128). LAG-2 is a critical component of the Notch signaling pathway, functioning as an activating ligand for the LIN-12 and GLP-1 Notch receptors during multiple developmental processes throughout the C. elegans life cycle.

Protein Structure and Molecular Function

Domain Architecture

LAG-2 is a single-pass transmembrane protein with a modular extracellular domain that mediates receptor binding. The protein contains several functionally distinct domains, detailed in the table below:

Domain Name Location/Position Structural Features Functional Role
MNNL/C2 domain N-terminal extracellular region; MNNL region is approximately 105 amino acids Predicted C2-like fold; canonical C2 domains form an eight-stranded antiparallel β-sandwich and can bind membrane phospholipids. LAG-2-specific calcium dependence remains unresolved. (holt2016characterisationofthe pages 102-108, holt2016characterisationofthe pages 50-55, feng2024thestructuraland pages 64-68) Required for productive LAG-2 signaling in functional-rescue experiments; likely provides a receptor-contact surface and helps orient or stabilize the ectodomain at the membrane. (holt2016characterisationofthe pages 50-55, holt2016characterisationofthe pages 55-60)
DSL domain Extracellular; immediately C-terminal to the MNNL/C2 region Defining Delta/Serrate/LAG-2 module containing six cysteines arranged into three disulfide bonds; adopts an EGF-related but distinct fold. (holt2016characterisationofthe pages 45-50) Essential Notch-receptor interaction and signaling module: deleting it abolishes rescue of Notch-related mutant phenotypes. It mediates engagement of LIN-12 and GLP-1, initiating receptor proteolysis and downstream signaling. (luo2020positiveautoregulationof pages 1-4, holt2016characterisationofthe pages 45-50)
EGF-like repeats Extracellular; downstream of the DSL domain and before the membrane-spanning segment Repeated, disulfide-stabilized EGF-like modules forming part of the elongated ectodomain; some canonical ligand EGF repeats can bind calcium. (holt2016characterisationofthe pages 102-108, feng2024thestructuraland pages 44-49) Support ectodomain architecture, receptor recognition, or presentation, but appear modulatory rather than strictly essential in LAG-2 because deletion of its EGF-like region did not abolish phenotypic rescue in the reported assays. (holt2016characterisationofthe pages 45-50, holt2016characterisationofthe pages 180-186)
Transmembrane domain Single membrane-spanning segment near the C terminus Hydrophobic anchor characteristic of a single-pass transmembrane DSL ligand. (holt2016characterisationofthe pages 102-108, feng2024thestructuraland pages 40-44) Retains LAG-2 at the signal-sending cell surface for juxtacrine signaling. Membrane association is functionally important: a soluble ectodomain did not rescue lag-2 null lethality, whereas GPI-mediated membrane tethering restored partial activity. (post2025notchactivityis pages 2-3, langridge2021thec.elegans pages 5-8)
Intracellular domain Short cytoplasmic C-terminal tail following the transmembrane segment Variable cytosolic region; unlike the conserved extracellular receptor-binding modules, no specific catalytic domain is established. (feng2024thestructuraland pages 44-49) May influence trafficking, ubiquitination, or endocytic regulation, but is dispensable for tested C. elegans signaling events: LAG-2 lacking its intracellular domain, or intracellular lysines used for ubiquitination, can still activate Notch because LIN-12 and GLP-1 have relatively low force thresholds. (langridge2021thec.elegans pages 8-12, langridge2021thec.elegans pages 1-5)

Table: Domain-level summary of the extracellular receptor-binding architecture, membrane anchor, and cytoplasmic tail of C. elegans LAG-2. The table distinguishes LAG-2-specific experimental evidence from functions inferred through conserved canonical Notch-ligand structure.

The MNNL/C2 domain at the N-terminus (approximately 105 amino acids) adopts a predicted C2-like fold and is essential for LAG-2 function, as deletion of this region abolishes rescue activity in genetic complementation experiments (holt2016characterisationofthe pages 50-55). This domain contributes to Notch receptor binding and likely helps orient the ligand at the membrane through phospholipid interactions (feng2024thestructuraland pages 44-49, feng2024thestructuraland pages 64-68). The DSL domain is the defining feature of canonical Notch ligands and contains six cysteine residues arranged in three disulfide bonds (holt2016characterisationofthe pages 45-50). Functional studies demonstrate that the DSL domain is absolutely required for LAG-2 activity: deletion mutants lacking this domain fail to rescue Notch-related phenotypes (holt2016characterisationofthe pages 45-50, holt2016characterisationofthe pages 180-186).

Molecular Mechanism of Notch Activation

LAG-2 functions as an activating ligand for Notch receptors through direct protein-protein interaction. When LAG-2 on a signal-sending cell binds to LIN-12 or GLP-1 on an adjacent cell, it triggers a series of proteolytic cleavages that release the Notch intracellular domain (NICD) (luo2020positiveautoregulationof pages 1-4, luo2020positiveautoregulationof pages 31-34). The released NICD translocates to the nucleus, where it associates with the DNA-binding protein LAG-1/CSL and co-activators to activate transcription of Notch target genes (luo2020positiveautoregulationof pages 1-4, chen2020glp1notch—lag1csl pages 2-4).

A distinctive feature of C. elegans LAG-2 compared to Drosophila and mammalian Notch ligands is its lower mechanical force requirement for receptor activation. Recent work by Langridge et al. (2021) demonstrated that LIN-12 and GLP-1 are tuned to lower force thresholds, allowing LAG-2 to activate these receptors without the strong Epsin-dependent endocytic pulling force required in other systems (langridge2021thec.elegans pages 8-12, langridge2021thec.elegans pages 5-8, langridge2021thec.elegans pages 1-5). Consequently, LAG-2 can signal effectively even when its intracellular domain is deleted or when ubiquitination sites are mutated, distinguishing it from canonical Drosophila Delta or mammalian Notch ligands (langridge2021thec.elegans pages 1-5, langridge2021thec.elegans pages 16-20). However, membrane tethering remains important: a secreted LAG-2 ectodomain alone does not rescue lag-2 null mutants, while GPI-anchored versions restore partial activity (langridge2021thec.elegans pages 5-8).

Binding Partners and Regulatory Interactions

LAG-2 interacts with multiple binding partners that modulate its activity:

  1. GLP-1 and LIN-12 Notch receptors: The primary substrates for LAG-2 signaling. LAG-2 binds the extracellular domain of these receptors to initiate signal transduction (post2025notchactivityis pages 2-3, post2025notchactivityis pages 5-7, luo2020positiveautoregulationof pages 1-4).

  2. LAT-1 (Latrophilin): A recent breakthrough discovery by Post et al. (2025) identified the adhesion GPCR LAT-1 as a direct binding partner of LAG-2 (post2025notchactivityis pages 5-7, post2025notchactivityis pages 8-9). This interaction occurs in cis (on the same cell) through LAT-1's RBL and GAIN domains and enhances Notch receptor activation through a G-protein-independent mechanism (post2025notchactivityis pages 8-9, post2025notchactivityis pages 7-8). LAT-1 appears to stabilize LAG-2 at the membrane or enhance its signaling capacity, thereby fine-tuning the strength of Notch pathway activation in the germline stem cell niche (post2025notchactivityis pages 8-9, post2025notchactivityis pages 2-3).

Subcellular Localization

LAG-2 is a membrane-bound protein localized to the plasma membrane of signal-sending cells, where it functions through direct cell-to-cell contact (juxtacrine signaling) (post2025notchactivityis pages 8-9, post2025notchactivityis pages 2-3, post2025notchactivityis pages 3-5). The protein is not secreted as a soluble ligand but remains anchored to the cell surface via its transmembrane domain (post2025notchactivityis pages 2-3). This membrane localization is functionally critical, as evidenced by the requirement for membrane association to achieve effective receptor activation (langridge2021thec.elegans pages 5-8).

LAG-2 is expressed in tissue- and context-specific patterns:

Biological Processes and Signaling Pathways

LAG-2 functions as a central ligand in the LIN-12/Notch and GLP-1/Notch signaling pathways, regulating multiple critical developmental processes:

Developmental Process Cell Type Expressing LAG-2 Notch Receptor Activated Direct Transcriptional Targets Biological Outcome
Germline stem-cell maintenance Distal tip cell (DTC), the somatic germline niche GLP-1 on adjacent distal germ cells lst-1 and sygl-1—the two strongly supported primary protein-coding targets in the germline Maintains the proliferative stem/progenitor pool and suppresses premature meiotic entry (chen2020glp1notch—lag1csl pages 2-4, chen2020glp1notch—lag1csl pages 12-14, chen2020glp1notch—lag1csl pages 11-12)
Anchor-cell/ventral-uterine-cell (AC/VU) specification Initially equivalent AC/VU precursor cells (Z1.ppp and Z4.aaa); LAG-2 becomes enriched in the presumptive AC LIN-12 on the neighboring presumptive VU cell Context-specific output includes direct positive autoregulation of lag-1 through LAG-1/CSL-binding sites; a complete AC/VU-specific direct-target set is not established Reciprocal ligand–receptor expression and lateral inhibition resolve two equivalent precursors into one signal-sending AC and one LIN-12-active VU; reduced LAG-2 can produce two ACs (luo2020positiveautoregulationof pages 1-4, holt2016characterisationofthe pages 128-134, luo2020positiveautoregulationof pages 7-10)
Vulval development Primary-fated vulval precursor P6.p, following LET-23/EGFR–Ras–MAPK induction LIN-12 on neighboring P5.p and P7.p Not fully defined for LAG-2 in this context; LIN-12 activation directly upregulates lag-1 and induces a broader secondary-fate transcriptional program Promotes secondary (2°) vulval fates in P5.p and P7.p and prevents inappropriate primary-fate adoption, establishing the normal 2°–1°–2° pattern (luo2020positiveautoregulationof pages 31-34)
Embryonic and early larval development Multiple context-dependent signal-sending cells LIN-12 and/or GLP-1, depending on the cell interaction No LAG-2-specific direct target set established in the cited evidence Required for Notch-dependent tissue specification, including rectum/anus formation and excretory-cell development; strong loss causes the characteristic Lag phenotype and L1 arrest (holt2016characterisationofthe pages 124-128)

Table: This table maps the principal developmental contexts in which membrane-bound LAG-2 activates C. elegans Notch receptors, distinguishing established direct targets from incompletely defined downstream programs.

Germline Stem Cell Maintenance

The most extensively characterized role of LAG-2 is in maintaining the germline stem cell population. The distal tip cell (DTC) presents LAG-2 to adjacent germ cells, activating the GLP-1 Notch receptor (chen2020glp1notch—lag1csl pages 2-4, post2025notchactivityis pages 1-2). A landmark study by Chen et al. (2020) used integrated genomic approaches (LAG-1/CSL ChIP-seq, GLP-1-dependent RNA-seq, and temporal LAG-1 depletion) to identify lst-1 and sygl-1 as the only strongly supported direct transcriptional targets of GLP-1/Notch signaling in the germline (chen2020glp1notch—lag1csl pages 12-14, chen2020glp1notch—lag1csl pages 16-17, chen2020glp1notch—lag1csl pages 1-2, chen2020glp1notch—lag1csl pages 11-12). These two genes redundantly promote the stem cell fate by repressing meiotic entry pathways, thereby maintaining a proliferative progenitor pool (chen2020glp1notch—lag1csl pages 2-4).

Recent work by Koitz et al. (2025) revealed that LAG-2 protein levels are dynamically regulated by nutritional status during dauer formation (koitz2025predauerstarvationdecouples pages 8-11, koitz2025predauerstarvationdecouples pages 11-13). During starvation-induced dauer entry, LAG-2 protein decreases rapidly in the DTC, contributing to germline quiescence. Remarkably, upon dauer exit, LAG-2 protein levels recover within approximately two hours through post-transcriptional mechanisms, preceding the restoration of germline proliferation (koitz2025predauerstarvationdecouples pages 11-13). This finding links environmental sensing to stem cell niche signaling and demonstrates sophisticated regulation of LAG-2 beyond simple transcriptional control.

Anchor Cell and Ventral Uterine Cell Specification

During somatic gonadal development, LAG-2 participates in a lateral inhibition process that specifies one anchor cell (AC) and one ventral uterine (VU) cell from two initially equivalent precursors (holt2016characterisationofthe pages 128-134, luo2020positiveautoregulationof pages 7-10). Initially, both Z1.ppp and Z4.aaa cells express both lag-2 and lin-12. Through reciprocal signaling, one cell increases LAG-2 expression while reducing LIN-12, becoming the signal-sending anchor cell, while the neighboring cell maintains high LIN-12 activity and adopts the VU fate (holt2016characterisationofthe pages 128-134). Loss or reduction of LAG-2 function disrupts this balance, resulting in the specification of two anchor cells instead of the normal AC/VU pair (holt2016characterisationofthe pages 128-134).

Luo et al. (2020) discovered that this process involves positive autoregulation of lag-1: LIN-12 activation by LAG-2 induces transcriptional upregulation of lag-1 through direct LAG-1/CSL binding sites, creating a feedback mechanism that stabilizes cell fate decisions (luo2020positiveautoregulationof pages 1-4, luo2020positiveautoregulationof pages 7-10).

Vulval Development

LAG-2 plays a key role in vulval precursor cell (VPC) patterning through lateral inhibition. Following induction of P6.p by EGF/LET-23/Ras-MAPK signaling to adopt the primary (1°) vulval fate, P6.p expresses DSL ligands including LAG-2 (luo2020positiveautoregulationof pages 31-34). LAG-2 then activates LIN-12 in the neighboring P5.p and P7.p cells, promoting their adoption of secondary (2°) vulval fates while preventing them from inappropriately adopting primary fates (luo2020positiveautoregulationof pages 31-34). This establishes the characteristic 2°–1°–2° pattern essential for proper vulval morphogenesis.

Embryonic and Larval Development

Loss-of-function lag-2 mutations produce severe embryonic and early larval defects. The characteristic "Lag" phenotype includes failure to form the rectum and anus, resulting in developmental arrest during the L1 larval stage (holt2016characterisationofthe pages 124-128). Additional defects include abnormal nose morphology and absence of the excretory cell, demonstrating LAG-2's essential role in multiple tissue specifications during embryogenesis (holt2016characterisationofthe pages 124-128). Temperature-sensitive alleles such as lag-2(q420) allow conditional analysis and reveal additional post-embryonic developmental requirements when animals are shifted to restrictive temperatures after L1 (holt2016characterisationofthe pages 124-128).

Recent Developments (2020-2026)

Year First author Key finding Significance
2020 Chen Integrated germline LAG-1/CSL ChIP-seq, GLP-1-dependent RNA-seq, and acute LAG-1-depletion data identified lst-1 and sygl-1 as the only strongly supported direct protein-coding GLP-1/Notch targets mediating germline stem-cell fate. (chen2020glp1notch—lag1csl pages 12-14, chen2020glp1notch—lag1csl pages 16-17, chen2020glp1notch—lag1csl pages 11-12) Defines the principal transcriptional output downstream of DTC-presented LAG-2 → GLP-1 signaling and connects ligand reception directly to maintenance of proliferative germ cells.
2020 Luo Showed that LIN-12 activation transcriptionally upregulates lag-1 through LAG-1/CSL-binding sites, establishing direct positive autoregulation during reproductive-system cell-fate decisions. (luo2020positiveautoregulationof pages 1-4, luo2020positiveautoregulationof pages 7-10) Reveals a feedback mechanism that can reinforce or stabilize the transcriptional response initiated by LAG-2–LIN-12 signaling.
2021 Langridge Found that the LIN-12 and GLP-1 negative regulatory regions are tuned to lower activation-force thresholds than Drosophila Notch; LAG-2 signaling can occur without its intracellular domain or Epsin-dependent endocytosis, although membrane tethering remains important. (langridge2021thec.elegans pages 8-12, langridge2021thec.elegans pages 5-8, langridge2021thec.elegans pages 1-5, langridge2021thec.elegans pages 16-20) Revises the mechanotransduction model for nematode Notch activation and explains how LAG-2 can activate receptors with less ligand-generated pulling force than canonical fly or vertebrate systems.
2024 Lv Reviewed the evolution, architecture, expression, and functions of Notch-pathway components across invertebrates, including DSL ligands such as C. elegans LAG-2. (lv2024evolutionandfunction pages 2-4) Places LAG-2 within the conserved yet evolutionarily adaptable DSL–Notch signaling system; this is comparative context rather than a LAG-2-specific experimental study.
2025 Post Demonstrated that the adhesion GPCR LAT-1 directly binds LAG-2 in cis through extracellular RBL/GAIN-region contacts and enhances GLP-1 activation through a G-protein-independent mechanism. (post2025notchactivityis pages 5-7, post2025notchactivityis pages 8-9, post2025notchactivityis pages 7-8) Identifies a previously unrecognized cell-surface modulator of LAG-2 activity that fine-tunes Notch signaling and proliferative-cell number in the gonadal stem-cell niche.
2025 Koitz Reported that DTC-associated LAG-2 protein decreases during starvation/dauer and rapidly returns during recovery—within approximately two hours—without a matching immediate transcriptional increase. (koitz2025predauerstarvationdecouples pages 8-11, koitz2025predauerstarvationdecouples pages 11-13) Supports rapid post-transcriptional or post-translational control of niche-presented LAG-2, linking nutritional history to germline quiescence, recovery, and later reproductive output; reported initially as a bioRxiv preprint.
2026 Kato Reported that the AGEF-1/ARF-1/AP-1 membrane-trafficking pathway regulates LIN-12/Notch signaling differently across somatic-gonad and vulval tissues; endogenous LAG-2 reporter abundance was altered during AC/VU specification. (kato2026theagef1arf1gtpaseap1 pages 9-13) Suggests that trafficking-dependent control of LAG-2/receptor abundance or localization is tissue-context dependent; because the work is a bioRxiv preprint and LAG-2 was used partly as an anchor-cell marker, direct regulation of LAG-2 trafficking remains provisional.

Table: Chronological summary of mechanistic and regulatory advances in LAG-2/Notch research from 2020 through 2026. The table distinguishes established findings from comparative reviews and provisional preprint evidence.

Several important advances have enhanced our understanding of LAG-2 function in recent years:

Novel regulatory mechanisms: The discovery that LAT-1 (latrophilin) directly binds LAG-2 in cis and modulates Notch signaling represents a paradigm shift in understanding Notch pathway regulation (post2025notchactivityis pages 5-7, post2025notchactivityis pages 8-9). This G-protein-independent mechanism fine-tunes signaling strength and demonstrates that Notch ligand activity can be modulated by cell-surface interactions beyond the canonical receptor.

Direct target identification: The Chen et al. (2020) study definitively established lst-1 and sygl-1 as the sole primary protein-coding transcriptional targets of GLP-1/Notch signaling in the germline (chen2020glp1notch—lag1csl pages 12-14, chen2020glp1notch—lag1csl pages 11-12), providing a complete molecular pathway from LAG-2 ligand presentation through receptor activation to transcriptional output.

Mechanical activation insights: The work by Langridge et al. (2021) revealed fundamental differences in mechanotransduction between C. elegans and other organisms, showing that LAG-2-mediated activation requires substantially less mechanical force than Drosophila or mammalian systems (langridge2021thec.elegans pages 8-12, langridge2021thec.elegans pages 1-5, langridge2021thec.elegans pages 22-28). This finding explains why LAG-2 can function without its intracellular domain and without Epsin-dependent endocytosis.

Post-transcriptional regulation: The Koitz et al. (2025) study demonstrated rapid, post-transcriptional regulation of LAG-2 protein levels in response to nutritional status (koitz2025predauerstarvationdecouples pages 8-11, koitz2025predauerstarvationdecouples pages 11-13), revealing an additional layer of control that couples environmental conditions to stem cell niche signaling.

Tissue-specific trafficking regulation: Preliminary evidence from Kato et al. (2026) suggests that the AGEF-1/ARF-1/AP-1 membrane trafficking pathway differentially regulates LAG-2 and LIN-12/Notch signaling in a tissue-specific manner (kato2026theagef1arf1gtpaseap1 pages 9-13), though these findings await peer review.

C. elegans possesses a second DSL ligand, APX-1, which shares functional overlap with LAG-2 but is not fully redundant (holt2016characterisationofthe pages 153-157, holt2016characterisationofthe pages 124-128). Both ligands can activate LIN-12 and GLP-1 receptors, and APX-1 can partially rescue lag-2 mutant phenotypes (holt2016characterisationofthe pages 153-157). However, they differ in developmental contexts and expression patterns: APX-1 was initially identified through its maternal role in early embryonic ABp blastomere specification, whereas LAG-2 functions prominently in later developmental processes (holt2016characterisationofthe pages 124-128). The DSL domains of the two ligands share some residues but lack a strictly conserved motif, suggesting possible differences in receptor-binding affinities (holt2016characterisationofthe pages 153-157, holt2016characterisationofthe pages 98-102). APX-1 can also bind LAT-1, suggesting that latrophilin-mediated modulation may be a general mechanism for C. elegans Notch ligands (post2025notchactivityis pages 7-8).

Expert Perspectives and Current Understanding

LAG-2 exemplifies the versatility of Notch signaling: the same ligand-receptor pair is deployed in multiple cellular contexts to generate distinct developmental outcomes through combinatorial regulation, tissue-specific cofactors, and varying signaling thresholds. The discovery of LAT-1 as a LAG-2 modulator represents an emerging theme in the field—that canonical signaling pathways are fine-tuned by auxiliary cell-surface proteins that adjust signal strength without altering core pathway logic (post2025notchactivityis pages 8-9).

The finding that C. elegans Notch receptors function at lower force thresholds has important implications for understanding Notch evolution and mechanism. As reviewed in multiple recent articles, this demonstrates that the mechanical requirements for Notch activation are not universal but rather have been tuned during evolution to match organismal and developmental contexts (langridge2021thec.elegans pages 8-12, langridge2021thec.elegans pages 22-28). This evolutionary plasticity in force requirements while maintaining conserved core signaling logic highlights the adaptability of the Notch pathway.

Conclusions

LAG-2 is a membrane-bound DSL-family Notch ligand essential for multiple developmental processes in C. elegans. Its primary molecular function is to bind and activate LIN-12 and GLP-1 Notch receptors on neighboring cells, initiating proteolytic release of the Notch intracellular domain and subsequent transcriptional activation of context-specific target genes. The protein localizes to the plasma membrane of signal-sending cells and mediates juxtacrine signaling in the germline stem cell niche, during AC/VU specification, in vulval patterning, and throughout embryonic development.

Recent research (2020-2026) has revealed sophisticated regulatory mechanisms controlling LAG-2 activity, including direct modulation by the LAT-1 aGPCR, rapid post-transcriptional regulation in response to nutritional status, and mechanistic differences in force-dependent activation compared to other organisms. The identification of lst-1 and sygl-1 as the sole direct germline targets of GLP-1/Notch signaling provides a complete molecular pathway in this key developmental context. These advances establish LAG-2 as a paradigm for understanding how evolutionarily conserved signaling ligands achieve developmental specificity through multiple layers of regulation while maintaining core mechanistic principles.

References

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  10. (feng2024thestructuraland pages 40-44): X Feng. The structural and functional significance of lipid-binding properties of human notch ligands. Unknown journal, 2024.

  11. (post2025notchactivityis pages 2-3): Willem Berend Post, Victoria Elisabeth Groß, Daniel Matúš, Iannis Charnay, Fabian Liessmann, Florian Seufert, Peter Hildebrand, Jens Meiler, Anette Kaiser, Torsten Schöneberg, and Simone Prömel. Notch activity is modulated by the agpcr latrophilin binding the dsl ligand in c. elegans. Nature Communications, Jul 2025. URL: https://doi.org/10.1038/s41467-025-61730-0, doi:10.1038/s41467-025-61730-0. This article has 4 citations and is from a highest quality peer-reviewed journal.

  12. (langridge2021thec.elegans pages 5-8): Paul D. Langridge, Jessica Yu Chan, Alejandro Garcia-Diaz, Iva Greenwald, and Gary Struhl. The c. elegans notch proteins lin-12 and glp-1 are tuned to lower force thresholds for activation than drosophila notch. bioRxiv, Feb 2021. URL: https://doi.org/10.1101/2021.02.11.429991, doi:10.1101/2021.02.11.429991. This article has 1 citations.

  13. (langridge2021thec.elegans pages 8-12): Paul D. Langridge, Jessica Yu Chan, Alejandro Garcia-Diaz, Iva Greenwald, and Gary Struhl. The c. elegans notch proteins lin-12 and glp-1 are tuned to lower force thresholds for activation than drosophila notch. bioRxiv, Feb 2021. URL: https://doi.org/10.1101/2021.02.11.429991, doi:10.1101/2021.02.11.429991. This article has 1 citations.

  14. (langridge2021thec.elegans pages 1-5): Paul D. Langridge, Jessica Yu Chan, Alejandro Garcia-Diaz, Iva Greenwald, and Gary Struhl. The c. elegans notch proteins lin-12 and glp-1 are tuned to lower force thresholds for activation than drosophila notch. bioRxiv, Feb 2021. URL: https://doi.org/10.1101/2021.02.11.429991, doi:10.1101/2021.02.11.429991. This article has 1 citations.

  15. (luo2020positiveautoregulationof pages 31-34): Katherine Leisan Luo, Ryan S. Underwood, and Iva Greenwald. Positive autoregulation of lag-1 in response to lin-12 activation in cell fate decisions during c. elegans reproductive system development. Development, Jan 2020. URL: https://doi.org/10.1242/dev.193482, doi:10.1242/dev.193482. This article has 14 citations and is from a domain leading peer-reviewed journal.

  16. (chen2020glp1notch—lag1csl pages 2-4): Jian Chen, Ariz Mohammad, Nanette Pazdernik, Huiyan Huang, Beth Bowman, Eric Tycksen, and Tim Schedl. Glp-1 notch—lag-1 csl control of the germline stem cell fate is mediated by transcriptional targets lst-1 and sygl-1. PLOS Genetics, 16:e1008650, Mar 2020. URL: https://doi.org/10.1371/journal.pgen.1008650, doi:10.1371/journal.pgen.1008650. This article has 61 citations and is from a domain leading peer-reviewed journal.

  17. (langridge2021thec.elegans pages 16-20): Paul D. Langridge, Jessica Yu Chan, Alejandro Garcia-Diaz, Iva Greenwald, and Gary Struhl. The c. elegans notch proteins lin-12 and glp-1 are tuned to lower force thresholds for activation than drosophila notch. bioRxiv, Feb 2021. URL: https://doi.org/10.1101/2021.02.11.429991, doi:10.1101/2021.02.11.429991. This article has 1 citations.

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Artifacts

Citations

  1. holt2016characterisationofthe pages 124-128
  2. holt2016characterisationofthe pages 45-50
  3. feng2024thestructuraland pages 44-49
  4. holt2016characterisationofthe pages 50-55
  5. post2025notchactivityis pages 2-3
  6. luo2020positiveautoregulationof pages 31-34
  7. koitz2025predauerstarvationdecouples pages 11-13
  8. holt2016characterisationofthe pages 128-134
  9. lv2024evolutionandfunction pages 2-4
  10. holt2016characterisationofthe pages 153-157
  11. post2025notchactivityis pages 7-8
  12. post2025notchactivityis pages 8-9
  13. luo2020positiveautoregulationof pages 1-4
  14. holt2016characterisationofthe pages 102-108
  15. feng2024thestructuraland pages 64-68
  16. holt2016characterisationofthe pages 55-60
  17. holt2016characterisationofthe pages 180-186
  18. feng2024thestructuraland pages 40-44
  19. post2025notchactivityis pages 5-7
  20. post2025notchactivityis pages 3-5
  21. post2025notchactivityis pages 1-2
  22. luo2020positiveautoregulationof pages 7-10
  23. koitz2025predauerstarvationdecouples pages 8-11
  24. holt2016characterisationofthe pages 98-102
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