Browse > Article
http://dx.doi.org/10.5483/BMBRep.2013.46.4.269

Clustered LAG-1 binding sites in lag-1/CSL are involved in regulating lag-1 expression during lin-12/Notch-dependent cell-fate specification  

Choi, Vit Na (Department of Molecular Bioscience, College of Biomedical Science, Kangwon National University)
Park, Seong Kyun (Department of Molecular Bioscience, College of Biomedical Science, Kangwon National University)
Hwang, Byung Joon (Department of Molecular Bioscience, College of Biomedical Science, Kangwon National University)
Publication Information
BMB Reports / v.46, no.4, 2013 , pp. 219-224 More about this Journal
Abstract
The cell-fate specification of the anchor cell (AC) and a ventral uterine precursor cell (VU) in Caenorhabditis elegans is initiated by a stochastic interaction between LIN-12/Notch receptor and LAG-2/Delta ligand in two neighboring Z1.ppp and Z4.aaa cells. Both cells express lin-12 and lag-2 before specification, and a small difference in LIN-12 activity leads to the exclusive expressions of lin-12 in VU and lag-2 in the AC, through a feedback mechanism of unknown nature. Here we show that the expression pattern of lag-1/CSL, a transcriptional repressor itself that turns into an activator upon binding of the intracellular domain of Notch, overlaps with that of lin-12. Site-directed mutagenesis of LAG-1 binding sites in lag-1 maintains its expression in the AC, and eliminates it in the VU. Thus, AC/VU cell-fate specification appears to involve direct regulation of lag-1 expression by the LAG-1 protein, activating its transcription in VU cells, but repressing it in the AC.
Keywords
Anchor cell/ventral uterine precursor cell; Cell-fate specification; CSL; Feedback loop; Notch signaling;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Hirsh, D., Oppenheim, D. and Klass, M. (1976) Development of the reproductive system of Caenorhabditis elegans. Dev. Biol. 49, 200-219.   DOI   ScienceOn
2 Kimble, J. and Hirsh, D. (1979) The postembryonic cell lineages of the hermaphrodite and male gonads in Caenorhabditis elegans. Dev. Biol. 70, 396-417.   DOI   ScienceOn
3 Brenner, S. (1974) The genetics of Caenorhabditis elegans. Genetics 77, 71-94.
4 Mello, C. C., Kramer, J. M., Stinchcomb, D. and Ambros, V. (1991) Efficient gene transfer in C. elegans: extrachromosomal maintenance and integration of transforming sequences. EMBO J. 10, 3959-3970.
5 Hobert, O. (2002) PCR fusion-based approach to create reporter gene constructs for expression analysis in transgenic C. elegans. Biotechniques 32, 728-730.
6 Segalen, M. and Bellaiche, Y. (2009) Cell division orientation and planar cell polarity pathways. Semin. Cell Dev. Biol. 20, 972-977.   DOI   ScienceOn
7 Guo, G., Huss, M., Tong, G. Q., Wang, C., Li Sun, L., Clarke, N. D. and Robson, P. (2010) Resolution of cell fate decisions revealed by single-cell gene expression analysis from zygote to blastocyst. Dev. Cell 18, 675-685.   DOI   ScienceOn
8 Bailey, A. M. and Posakony, J. W. (1995) Suppressor of hairless directly activates transcription of enhancer of split complex genes in response to Notch receptor activity. Genes Dev. 9, 2609-2622.   DOI   ScienceOn
9 Castro, B., Barolo, S., Bailey, A. M. and Posakony, J. W. (2005) Lateral inhibition in proneural clusters: cis-regulatory logic and default repression by Suppressor of Hairless. Development 132, 3333-3344.   DOI   ScienceOn
10 Kimble, J. and Simpson, P. (1997) The LIN-12/Notch signaling pathway and its regulation. Annu. Rev. Cell Dev. Biol. 13, 333-361.   DOI   ScienceOn
11 Wilkinson, H. A., Fitzgerald, K. and Greenwald, I. (1994) Reciprocal changes in expression of the receptor lin-12 and its ligand lag-2 prior to commitment in a C. elegans cell fate decision. Cell 79, 1187-1198.   DOI   ScienceOn
12 Seydoux, G. and Greenwald, I. (1989) Cell autonomy of lin-12 function in a cell fate decision in C. elegans. Cell 57, 1237-1245.   DOI   ScienceOn
13 Hwang, B. J., Meruelo, A. D. and Sternberg, P. W. (2007) C. elegans EVI1 proto-oncogene, EGL-43, is necessary for Notch-mediated cell fate specification and regulates cell invasion. Development 134, 669-679.   DOI   ScienceOn
14 Johnston, R. J., Jr. and Desplan, C. (2010) Stochastic mechanisms of cell fate specification that yield random or robust outcomes. Annu. Rev. Cell Dev. Biol. 26, 689-719.   DOI   ScienceOn
15 Greenwald, I. (1998) LIN-12/Notch signaling: lessons from worms and flies. Genes Dev. 12, 1751-1762.   DOI   ScienceOn
16 Greenwald, I. (2012) Notch and the awesome power of genetics. Genetics 191, 655-669.   DOI
17 Hwang, B. J. and Sternberg, P. W. (2004) A cell-specific enhancer that specifies lin-3 expression in the C. elegans anchor cell for vulval development. Development 131, 143-151.   DOI   ScienceOn
18 Christensen, S., Kodoyianni, V., Bosenberg, M., Friedman, L. and Kimble, J. (1996) lag-1, a gene required for lin-12 and glp-1 signaling in Caenorhabditis elegans, is homologous to human CBF1 and Drosophila Su(H). Development 122, 1373-1383.
19 Zimber-Strobl, U., Strobl, L. J., Meitinger, C., Hinrichs, R., Sakai, T., Furukawa, T., Honjo, T. and Bornkamm, G. W. (1994) Epstein-Barr virus nuclear antigen 2 exerts its transactivating function through interaction with recombination signal binding protein RBP-J kappa, the homologue of Drosophila Suppressor of Hairless. EMBO J. 13, 4973-4982.
20 Petcherski, A. G. and Kimble, J. (2000) LAG-3 is a putative transcriptional activator in the C. elegans Notch pathway. Nature 405, 364-368.   DOI   ScienceOn
21 Lee, M. H., Hook, B., Lamont, L. B., Wickens, M. and Kimble, J. (2006) LIP-1 phosphatase controls the extent of germline proliferation in Caenorhabditis elegans. EMBO J. 25, 88-96.   DOI   ScienceOn
22 Schuurmans, C. and Guillemot, F. (2002) Molecular mechanisms underlying cell fate specification in the developing telencephalon. Curr. Opin. Neurobiol. 12, 26-34.   DOI   ScienceOn
23 Artavanis-Tsakonas, S., Rand, M. D. and Lake, R. J. (1999) Notch signaling: cell fate control and signal integration in development. Science 284, 770-776.   DOI   ScienceOn
24 Rohrschneider, M. R. and Nance, J. (2009) Polarity and cell fate specification in the control of Caenorhabditis elegans gastrulation. Dev. Dyn. 238, 789-796.   DOI   ScienceOn