lag-2 encodes a DSL-family transmembrane ligand of Caenorhabditis elegans, related to the mammalian Jagged/Serrate class (JAG1, JAG2). It is expressed in the somatic distal tip cell, where it activates GLP-1/Notch in the adjacent germ cells and holds them in the mitotic stem cell state.
The same ligand is used elsewhere: it provides the anchor cell signal in the AC/VU decision and, together with APX-1 and DSL-1, contributes redundantly to the vulval lateral signal. That reuse across stages is why conditional configurations matter here. CD BioSciences delivers custom lag-2 alleles — knockouts, conditional and temperature-sensitive configurations, DSL-domain point mutants, human-variant knockins, and fluorescent or epitope tag knockins — with full genotype verification.
| Gene symbol | lag-2 (DSL-family transmembrane Notch ligand) |
|---|---|
| Protein product | LAG-2 — DSL-family transmembrane Notch ligand |
| Mammalian homolog | JAG1 / JAG2 (Jagged / Serrate class) |
| Biological role | A transmembrane DSL ligand of Caenorhabditis elegans, related to the mammalian Jagged/Serrate class. It is expressed by the somatic distal tip cell and acts as the niche signal that activates GLP-1/Notch in adjacent germ cells, holding them in the mitotic stem cell state. The same ligand is redeployed for the anchor cell / ventral uterine precursor decision and, redundantly with APX-1 and DSL-1, for the vulval lateral signal. |
| Loss-of-function phenotype | Reducing lag-2 activity causes germ cells to leave the mitotic cycle and enter meiosis prematurely, giving the Glp sterile phenotype. In the somatic gonad the AC/VU decision fails and both cells become anchor cells. Temperature-sensitive alleles such as q420ts additionally reveal LIN-12(0)-like defects in the postembryonic M lineage, where ventral cells that should become sex myoblasts become coelomocytes instead. |
| Why edit it | The distal tip cell / LAG-2 / GLP-1 axis is the canonical example of a stem cell niche: one somatic cell, one ligand, one receptor, and a graded response that positions the boundary between self-renewal and differentiation. It is also the clearest system for studying how a ligand deployed at one stage is reused at others, since the same gene acts in the embryo, the somatic gonad, and the vulva. |
| Recommended background | N2 (wild type). Because the germline role is essential for fertility, we recommend temperature-sensitive or conditional configurations for stage-specific questions, and scoring both the germline and somatic gonad phenotypes. |
| Representative allele | Classic temperature-sensitive alleles q411ts and q420ts; custom CRISPR nulls, conditional configurations, DSL-domain point mutants, and tag knockins available on request. |
lag-2 at a glance: lag-2 is the niche ligand that keeps germ cells mitotic; reducing it triggers premature meiosis and sterility. Editing lag-2 alone is a powerful way to dissect LAG-2 function in vivo, with conserved relevance to human JAG1 biology.
gRNA-guided Cas9 cutting with NHEJ repair to introduce frameshift indels, generating premature stop codons and null / strong-loss-of-function lag-2 alleles.
Homology-directed repair (HDR) inserts GFP / HA / FLAG or other tags at the lag-2 locus for endogenous expression and subcellular localization studies.
Introduce specific amino-acid substitutions to dissect functional domains and separate catalytic from scaffolding roles of LAG-2.
Build tissue-specific, inducible, or temperature-sensitive configurations and reporter lines for spatiotemporal analysis of LAG-2 function.
Plan for the fact that this ligand is used more than once. A straight null removes the germline, AC/VU and vulval inputs together, so if you want to separate them, use a conditional configuration or a temperature-sensitive allele and shift at the relevant stage. Tagged alleles are also useful here: LAG-2 localization at the distal tip cell membrane is itself a readable output.
Define target (knockout / knockin / point mutation), select gRNA(s) and HDR template, confirm against the latest genome build.
Design, validate, and synthesize high-specificity guide RNAs targeting the lag-2 locus.
Build Cas9 / gRNA delivery construct and, for knockin, the homology-arm repair template.
Perform gonadal microinjection of N2 animals with CRISPR components and co-CRISPR selection markers.
PCR, Sanger / sequencing, and phenotype confirmation to isolate edited animals and verify alleles.
Provide homozygous / balanced lag-2 strains plus a full genotype and methods report.
Standard knockout projects deliver a frameshift indel allele predicted to produce a premature stop and a loss-of-function phenotype. We confirm the edit by sequencing and, where relevant, by characteristic phenotype assays.
Yes. Using HDR with a designed repair template, we can insert GFP, HA, or FLAG tags at the C- or N-terminus while preserving endogenous promoter and regulation.
Timelines vary with editing type and validation needs, but our optimized pipeline and co-CRISPR selection typically shorten turnaround versus conventional approaches. Contact us with your design for a project-specific estimate.
Because C. elegans reuses a small set of signalling components in many contexts. LAG-2 is presented by whichever cell needs to signal at that moment — the distal tip cell for germline stem cells, the anchor cell precursor for the AC/VU decision, and the primary vulval precursor for the lateral signal. The consequence for experiment design is that a null is pleiotropic, and stage- or tissue-specific configurations are usually needed to ask a clean question. In the vulva specifically, LAG-2, APX-1 and DSL-1 act redundantly, so single ligand knockouts there are often near-normal.
CD BioSciences is committed to convenient, efficient, and cost-effective C. elegans model customization. Tell us your target design — knockout, knockin, tagging, or point mutation — and our scientists will respond with a tailored plan and quote.
Contact UsReferences
1. Kim H. M., Colaiácovo M. P. CRISPR-Cas9-guided genome engineering in C. elegans. Current Protocols in Molecular Biology, 2016, 115(1): 31.7.1–31.7.18.
2. Henderson S. T., Gao D., Lambie E. J., Kimble J. lag-2 may encode a signaling ligand for the GLP-1 and LIN-12 receptors of C. elegans. Development, 1994, 120(10): 2913–2924.
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