lin 12


Gene Symbol: lin 12
Description: Protein lin-12
Alias: Protein lin-12
Species: Caenorhabditis elegans

Top Publications

  1. Greenwald I, Seydoux G. Analysis of gain-of-function mutations of the lin-12 gene of Caenorhabditis elegans. Nature. 1990;346:197-9 pubmed
    ..These data suggest that self-association of the putative lin-12-encoded receptor leads to its activation, and that certain gain-of-function mutations result in ligand-independent activation. ..
  2. Yoo A, Greenwald I. LIN-12/Notch activation leads to microRNA-mediated down-regulation of Vav in C. elegans. Science. 2005;310:1330-3 pubmed
    ..Our results suggest that lin-12, mir-61, and vav-1 form a feedback loop that helps maximize lin-12 activity in the presumptive 2 degrees VPCs. ..
  3. Yochem J, Weston K, Greenwald I. The Caenorhabditis elegans lin-12 gene encodes a transmembrane protein with overall similarity to Drosophila Notch. Nature. 1988;335:547-50 pubmed
  4. Greenwald I, Sternberg P, Horvitz H. The lin-12 locus specifies cell fates in Caenorhabditis elegans. Cell. 1983;34:435-44 pubmed
    ..We propose that lin-12 functions as a binary switch to control decisions between alternative cell fates during C. elegans development...
  5. Sundaram M, Greenwald I. Suppressors of a lin-12 hypomorph define genes that interact with both lin-12 and glp-1 in Caenorhabditis elegans. Genetics. 1993;135:765-83 pubmed
    ..These sel genes may therefore function in both lin-12 and glp-1 mediated cell fate decisions. ..
  6. Struhl G, Fitzgerald K, Greenwald I. Intrinsic activity of the Lin-12 and Notch intracellular domains in vivo. Cell. 1993;74:331-45 pubmed
    ..Our results also suggest that equivalent truncated forms of lin-12/Notch family members in vertebrates, including known oncogenes, are similarly active. ..
  7. Hubbard E, Wu G, Kitajewski J, Greenwald I. sel-10, a negative regulator of lin-12 activity in Caenorhabditis elegans, encodes a member of the CDC4 family of proteins. Genes Dev. 1997;11:3182-93 pubmed
    ..We propose that SEL-10 promotes the ubiquitin-mediated turnover of LIN-12/Notch proteins, and discuss potential roles for the regulation of lin-12/Notch activity by sel-10 in cell fate decisions and tumorigenesis. ..
  8. Levitan D, Greenwald I. LIN-12 protein expression and localization during vulval development in C. elegans. Development. 1998;125:3101-9 pubmed
    ..We propose that downregulation of LIN-12 stability or translation in response to inductive signalling helps impose a bias on lateral signalling and contributes to the invariant pattern of VPC fates...
  9. Shaye D, Greenwald I. LIN-12/Notch trafficking and regulation of DSL ligand activity during vulval induction in Caenorhabditis elegans. Development. 2005;132:5081-92 pubmed

More Information


  1. de Souza N, Vallier L, Fares H, Greenwald I. SEL-2, the C. elegans neurobeachin/LRBA homolog, is a negative regulator of lin-12/Notch activity and affects endosomal traffic in polarized epithelial cells. Development. 2007;134:691-702 pubmed
    ..Our results also suggest that sel-2 activity may contribute to the appropriate steady-state level of LIN-12 or to trafficking events that affect receptor activation. ..
  2. Yoo A, Bais C, Greenwald I. Crosstalk between the EGFR and LIN-12/Notch pathways in C. elegans vulval development. Science. 2004;303:663-6 pubmed
    ..Subsequently, this effect is counteracted by the expression of multiple new negative regulators of the EGFR-MAPK pathway, under direct transcriptional control of the LIN-12-mediated lateral signal. ..
  3. Lambie E, Kimble J. Two homologous regulatory genes, lin-12 and glp-1, have overlapping functions. Development. 1991;112:231-40 pubmed
    ..We speculate that the lin-12 and glp-1 proteins are biochemically interchangeable and that their divergent roles in development may rely largely on differences in gene expression. ..
  4. Foehr M, Liu J. Dorsoventral patterning of the C. elegans postembryonic mesoderm requires both LIN-12/Notch and TGFbeta signaling. Dev Biol. 2008;313:256-66 pubmed
    ..Our work provides a model for how combined Notch and TGFbeta signaling regulates the developmental potential of two equipotent cells along the dorsoventral axis. ..
  5. Shaye D, Greenwald I. Endocytosis-mediated downregulation of LIN-12/Notch upon Ras activation in Caenorhabditis elegans. Nature. 2002;420:686-90 pubmed
    ..We also show that if LIN-12 is stabilized in P6.p, lateral signalling is compromised, indicating that LIN-12 downregulation is important in the appropriate specification of cell fates in vivo. ..
  6. Seydoux G, Greenwald I. Cell autonomy of lin-12 function in a cell fate decision in C. elegans. Cell. 1989;57:1237-45 pubmed
    ..We present a model in which lin-12 functions in the receiving mechanism for the "AC-to-VU" signal leading to the specification of the AC and VU fates of Z1.ppp and ..
  7. Ferguson E, Horvitz H. Identification and characterization of 22 genes that affect the vulval cell lineages of the nematode Caenorhabditis elegans. Genetics. 1985;110:17-72 pubmed
    ..Our results suggest that we may have identified most, or all, genes of these two classes...
  8. Regos A, Lengyel K, Takacs Vellai K, Vellai T. Identification of novel cis-regulatory regions from the Notch receptor genes lin-12 and glp-1 of Caenorhabditis elegans. Gene Expr Patterns. 2013;13:66-77 pubmed publisher
    ..The latter regulatory element is highly conserved in the paralogous glp-1 genomic environment, suggesting redundant developmental and physiological roles for the two Notch paralogs in the C. elegans nervous system. ..
  9. Walhout A, Sordella R, Lu X, Hartley J, Temple G, Brasch M, et al. Protein interaction mapping in C. elegans using proteins involved in vulval development. Science. 2000;287:116-22 pubmed
    ..A protein interaction mapping project is now feasible for C. elegans on a genome-wide scale and should contribute to the understanding of molecular mechanisms in this organism and in human diseases. ..
  10. Li J, Greenwald I. LIN-14 inhibition of LIN-12 contributes to precision and timing of C. elegans vulval fate patterning. Curr Biol. 2010;20:1875-9 pubmed publisher
  11. Liu Z, Shi H, Szymczak L, Aydin T, Yun S, Constas K, et al. Promotion of bone morphogenetic protein signaling by tetraspanins and glycosphingolipids. PLoS Genet. 2015;11:e1005221 pubmed publisher
  12. Hwang B, Meruelo A, Sternberg P. C. elegans EVI1 proto-oncogene, EGL-43, is necessary for Notch-mediated cell fate specification and regulates cell invasion. Development. 2007;134:669-79 pubmed
    ..Thus, egl-43 integrates temporally distinct upstream regulatory events and helps program cell fate specification and cell invasion. ..
  13. Tischler J, Lehner B, Chen N, Fraser A. Combinatorial RNA interference in Caenorhabditis elegans reveals that redundancy between gene duplicates can be maintained for more than 80 million years of evolution. Genome Biol. 2006;7:R69 pubmed
  14. Petcherski A, Kimble J. LAG-3 is a putative transcriptional activator in the C. elegans Notch pathway. Nature. 2000;405:364-8 pubmed
    ..elegans. We propose that GLP-1 and LIN-12 promote signalling by recruiting LAG-3 to target promoters, where it functions as a transcriptional activator. ..
  15. Solomon A, Mian Y, Ortega Cava C, Liu V, Gurumurthy C, Naramura M, et al. Upregulation of the let-7 microRNA with precocious development in lin-12/Notch hypermorphic Caenorhabditis elegans mutants. Dev Biol. 2008;316:191-9 pubmed publisher
    ..Importantly, the human microRNA let-7a was also upregulated in various human cell lines in response to Notch 1 activation, suggesting an evolutionarily conserved cross-talk between let-7 and the canonical lin-12/Notch signaling pathway. ..
  16. Li P, Collins K, Koelle M, Shen K. LIN-12/Notch signaling instructs postsynaptic muscle arm development by regulating UNC-40/DCC and MADD-2 in Caenorhabditis elegans. elife. 2013;2:e00378 pubmed publisher
    ..Therefore, the LIN-12/Notch signaling specifies target selection by selectively up-regulating guidance molecules and forming muscle arms in target cells. DOI: ..
  17. Singh K, Chao M, Somers G, Komatsu H, Corkins M, Larkins Ford J, et al. C. elegans Notch signaling regulates adult chemosensory response and larval molting quiescence. Curr Biol. 2011;21:825-34 pubmed publisher
    ..elegans in response to environmental stress. Additionally, Notch signaling regulates sleep-like quiescence in C. elegans, suggesting that Notch may regulate sleep in other species. ..
  18. Kovall R, Hendrickson W. Crystal structure of the nuclear effector of Notch signaling, CSL, bound to DNA. EMBO J. 2004;23:3441-51 pubmed
    ..A hydrophobic pocket on BTD is identified as the likely site of Notch interaction with CSL, which has functional implications for the mechanism of Notch signaling. ..
  19. Safdar K, Gu A, Xu X, Au V, Taylor J, Flibotte S, et al. UBR-5, a Conserved HECT-Type E3 Ubiquitin Ligase, Negatively Regulates Notch-Type Signaling in Caenorhabditis elegans. G3 (Bethesda). 2016;6:2125-34 pubmed publisher
    ..UBR-5 acts redundantly with SEL-10 to limit Notch signaling in certain tissues. We hypothesize that UBR-5 activity limits Notch-type signaling by promoting turnover of receptor or limiting its interaction with pathway components. ..
  20. Oommen K, Newman A. Co-regulation by Notch and Fos is required for cell fate specification of intermediate precursors during C. elegans uterine development. Development. 2007;134:3999-4009 pubmed
    ..We show that FOS-1 is expressed at pi cell specification and can bind in vitro to egl-13 upstream regulatory sequence (URS) as a heterodimer with C. elegans Jun...
  21. Green J, Inoue T, Sternberg P. The C. elegans ROR receptor tyrosine kinase, CAM-1, non-autonomously inhibits the Wnt pathway. Development. 2007;134:4053-62 pubmed
    ..A sequestration model is supported by our findings that the CAM-1 ECD binds to several Wnts in vitro. These results demonstrate how ROR proteins help to refine the spatial pattern of Wnt activity in a complex multicellular environment...
  22. Komatsu H, Chao M, Larkins Ford J, Corkins M, Somers G, Tucey T, et al. OSM-11 facilitates LIN-12 Notch signaling during Caenorhabditis elegans vulval development. PLoS Biol. 2008;6:e196 pubmed publisher
    ..We hypothesize that C. elegans OSM-11 and homologous proteins act as coactivators for Notch receptors, allowing precise regulation of Notch receptor signaling in developmental programs in both vertebrates and invertebrates. ..
  23. Sarov M, Murray J, Schanze K, Pozniakovski A, Niu W, Angermann K, et al. A genome-scale resource for in vivo tag-based protein function exploration in C. elegans. Cell. 2012;150:855-66 pubmed publisher
    ..We illustrate the utility of the resource by systematic chromatin immunopurification and automated 4D imaging, which produced detailed DNA binding and cell/tissue distribution maps for key transcription factor proteins. ..
  24. Nusser Stein S, Beyer A, Rimann I, Adamczyk M, Piterman N, Hajnal A, et al. Cell-cycle regulation of NOTCH signaling during C. elegans vulval development. Mol Syst Biol. 2012;8:618 pubmed publisher
    ..Our findings reveal a synchronization mechanism that coordinates NOTCH signaling with cell-cycle progression and thus permits the formation of a stable cell fate pattern. ..
  25. Hsu V, Zobel C, Lambie E, Schedl T, Kornfeld K. Caenorhabditis elegans lin-45 raf is essential for larval viability, fertility and the induction of vulval cell fates. Genetics. 2002;160:481-92 pubmed
    ..elegans development. ..
  26. Park S, Choi V, Hwang B. LIN-12/Notch regulates lag-1 and lin-12 expression during anchor cell/ventral uterine precursor cell fate specification. Mol Cells. 2013;35:249-54 pubmed publisher
    ..Ectopic expression of lag-1 cDNA in the AC causes a defect in the vulvaluterine (V-U) connection; therefore, LAG-1 should be eliminated in the AC to form a normal V-U connection at a later developmental stage in wild-type animals. ..
  27. Chao M, Larkins Ford J, Tucey T, Hart A. lin-12 Notch functions in the adult nervous system of C. elegans. BMC Neurosci. 2005;6:45 pubmed
    ..This is consistent with a role for Notch signaling in neurological disease with late onset symptoms. ..
  28. Choi M, Yoo A, Greenwald I. sel-11 and cdc-42, two negative modulators of LIN-12/Notch activity in C. elegans. PLoS ONE. 2010;5:e11885 pubmed publisher
    ..Our results underscore the multiplicity of negative regulatory mechanisms that impact on lin-12/Notch activity and suggest novel mechanisms by which constitutive lin-12/Notch activity might be exacerbated in cancer. ..
  29. Tian C, Shi H, Colledge C, Stern M, Waterston R, Liu J. The C. elegans SoxC protein SEM-2 opposes differentiation factors to promote a proliferative blast cell fate in the postembryonic mesoderm. Development. 2011;138:1033-43 pubmed publisher
    ..elegans M lineage suggests a possible more general link between Hox-PBC factors and SoxC proteins in regulating cell proliferation. ..
  30. Ouellet J, Li S, Roy R. Notch signalling is required for both dauer maintenance and recovery in C. elegans. Development. 2008;135:2583-92 pubmed publisher
    ..Then, as growth conditions improve, activation of the LIN-12 Notch receptor cooperates with the insulin-like signalling pathway to signal recovery from the dauer stage. ..
  31. Hale J, Amin N, George C, Via Z, Shi H, Liu J. A role of the LIN-12/Notch signaling pathway in diversifying the non-striated egg-laying muscles in C. elegans. Dev Biol. 2014;389:137-48 pubmed publisher
    ..elegans egg-laying system. We also identify multiple new factors that play critical roles in the proper specification of the different types of egg-laying muscles. ..
  32. Sallee M, Aydin T, Greenwald I. Influences of LIN-12/Notch and POP-1/TCF on the Robustness of Ventral Uterine Cell Fate Specification in Caenorhabditis elegans Gonadogenesis. G3 (Bethesda). 2015;5:2775-82 pubmed publisher
    ..elegans TCF ortholog, influences βVU fate. We propose a model for how Wnt and LIN-12/Notch signaling together lead to robust specification of the βVU fate. ..