Clustered LAG-1 binding sites in lag-1/CSL are involved in regulating lag-1 expression during lin-12/Notch-dependent cell-fate specification
0
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
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-1maintains 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.
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-1maintains 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.
참고문헌 (24)
- Artavanis-Tsakonas, S., "Notch signaling: cell fate control and signal integration in development", Science, 284, pp.770~776 (1999)
- Rohrschneider, M. R, "Polarity and cell fate specification in the control of Caenorhabditis elegans gastrulation", Dev. Dyn, 238, pp.789~796 (2009)
- Schuurmans, C., "Molecular mechanisms underlying cell fate specification in the developing telencephalon", Curr. Opin. Neurobiol, 12, pp.26~34 (2002)
- Segalen, M., "Cell division orientation and planar cell polarity pathways", Semin. Cell Dev. Biol, 20, pp.972~977 (2009)
- Guo, G., "Resolution of cell fate decisions revealed by single-cell gene expression analysis from zygote to blastocyst", Dev. Cell, 18, pp.675~685 (2010)
- Bailey, A. M, "Suppressor of hairless directly activates transcription of enhancer of split complex genes in response to Notch receptor activity", Genes Dev, 9, pp.2609~2622 (1995)
- Castro, B., "Lateral inhibition in proneural clusters: cis-regulatory logic and default repression by Suppressor of Hairless", Development, 132, pp.3333~3344 (2005)
- Kimble, J, "The LIN-12", Notch signaling pathway and its regulation, 1997, pp.13, 333~361
- Wilkinson, H. A., "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, pp.1187~1198 (1994)
- Seydoux, G., "Cell autonomy of lin-12 function in a cell fate decision in C. elegans", Cell, 57, pp.1237~1245 (1989)
- Johnston, R. J., Jr, "Stochastic mechanisms of cell fate specification that yield random or robust outcomes", Annu. Rev. Cell Dev. Biol, 26, pp.689~719 (2010)
- Greenwald, I., "LIN-12", Notch signaling: lessons from worms and flies, 1998, pp.12, 1751~1762
- Greenwald, I., "Notch and the awesome power of genetics", Genetics, 191, pp.655~669 (2012)
- Hwang, B. J., "C. elegans EVI1 proto-oncogene, EGL-43, is necessary for Notch-mediated cell fate specification and regulates cell invasion", Development, 134, pp.669~679 (2007)
- Hwang, B. J., "A cell-specific enhancer that specifies lin-3 expression in the C. elegans anchor cell for vulval development", Development, 131, pp.143~151 (2004)
- Christensen, S., "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, pp.1373~1383 (1996)
- Zimber-Strobl, U., "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, pp.4973~4982 (1994)
- Petcherski, A. G, "LAG-3 is a putative transcriptional activator in the C. elegans Notch pathway", Nature, 405, pp.364~368 (2000)
- Lee, M. H., "LIP-1 phosphatase controls the extent of germline proliferation in Caenorhabditis elegans", EMBO J, 25, pp.88~96 (2006)
- Hirsh, D., "Development of the reproductive system of Caenorhabditis elegans", Dev. Biol, 49, pp.200~219 (1976)
- Kimble, J., "The postembryonic cell lineages of the hermaphrodite and male gonads in Caenorhabditis elegans", Dev. Biol, 70, pp.396~417 (1979)
- Brenner, S., "The genetics of Caenorhabditis elegans", Genetics, 77, pp.71~94 (1974)
- Mello, C. C., "Efficient gene transfer in C. elegans: extrachromosomal maintenance and integration of transforming sequences", EMBO J, 10, pp.3959~3970 (1991)
- Hobert, O., "PCR fusion-based approach to create reporter gene constructs for expression analysis in transgenic C. elegans", Biotechniques, 32, pp.728~730 (2002)