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A microRNA controlling left/right neuronal asymmetry in Caenorhabditis elegans

Nature volume 426, pages 845–849 (2003)Cite this article

Abstract

How left/right functional asymmetry is layered on top of an anatomically symmetrical nervous system is poorly understood. In the nematode Caenorhabditis elegans, two morphologically bilateral taste receptor neurons, ASE left (ASEL) and ASE right (ASER), display a left/right asymmetrical expression pattern of putative chemoreceptor genes that correlates with a diversification of chemosensory specificities1,2. Here we show that a previously undefined microRNA termed lsy-6 controls this neuronal left/right asymmetry of chemosensory receptor expression. lsy-6 mutants that we retrieved from a genetic screen for defects in neuronal left/right asymmetry display a loss of the ASEL-specific chemoreceptor expression profile with a concomitant gain of the ASER-specific profile. A lsy-6 reporter gene construct is expressed in less than ten neurons including ASEL, but not ASER. lsy-6 exerts its effects on ASEL through repression of cog-1, an Nkx-type homeobox gene, which contains a lsy-6 complementary site in its 3′ untranslated region and that has been shown to control ASE-specific chemoreceptor expression profiles3. lsy-6 is the first microRNA to our knowledge with a role in neuronal patterning, providing new insights into left/right axis formation.

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Figure 1: lsy-6 regulates asymmetrical chemoreceptor gene expression.
Figure 2: lsy-6 encodes a novel miRNA.
Figure 3: lsy-6 acts in a highly tissue-specific manner.
Figure 4: lsy-6 represses cog-1 to promote ASEL cell fate.

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References

  1. Yu, S., Avery, L., Baude, E. & Garbers, D. L. Guanylyl cyclase expression in specific sensory neurons: a new family of chemosensory receptors. Proc. Natl Acad. Sci. USA 94, 3384–3387 (1997)

    Article  ADS  CAS  Google Scholar 

  2. Pierce-Shimomura, J. T., Faumont, S., Gaston, M. R., Pearson, B. J. & Lockery, S. R. The homeobox gene lim-6 is required for distinct chemosensory representations in C. elegans. Nature 410, 694–698 (2001)

    Article  ADS  CAS  Google Scholar 

  3. Chang, S., Johnston, R. J. Jr & Hobert, O. A transcriptional regulatory cascade that controls left/right asymmetry in chemosensory neurons of C. elegans. Genes Dev. 17, 2123–2137 (2003)

    Article  CAS  Google Scholar 

  4. Halpern, M. E., Liang, J. O. & Gamse, J. T. Leaning to the left: laterality in the zebrafish forebrain. Trends Neurosci. 26, 308–313 (2003)

    Article  CAS  Google Scholar 

  5. Yost, H. J. Left-right development from embryos to brains. Dev. Genet. 23, 159–163 (1998)

    Article  CAS  Google Scholar 

  6. Hobert, O., Johnston, R. J. Jr & Chang, S. Left-right asymmetry in the nervous system: the Caenorhabditis elegans model. Nature Rev. Neurosci. 3, 629–640 (2002)

    Article  CAS  Google Scholar 

  7. Bargmann, C. I. & Horvitz, H. R. Chemosensory neurons with overlapping functions direct chemotaxis to multiple chemicals in C. elegans. Neuron 7, 729–742 (1991)

    Article  CAS  Google Scholar 

  8. White, J. G., Southgate, E., Thomson, J. N. & Brenner, S. The structure of the nervous system of the nematode Caenorhabditis elegans. Phil. Trans. R. Soc. Lond. B 314, 1–340 (1986)

    Article  ADS  CAS  Google Scholar 

  9. Hobert, O., Tessmar, K. & Ruvkun, G. The Caenorhabditis elegans lim-6 LIM homeobox gene regulates neurite outgrowth and function of particular GABAergic neurons. Development 126, 1547–1562 (1999)

    CAS  PubMed  Google Scholar 

  10. Troemel, E. R., Sagasti, A. & Bargmann, C. I. Lateral signaling mediated by axon contact and calcium entry regulates asymmetric odorant receptor expression in C. elegans. Cell 99, 387–398 (1999)

    Article  CAS  Google Scholar 

  11. Wicks, S. R., Yeh, R. T., Gish, W. R., Waterston, R. H. & Plasterk, R. H. Rapid gene mapping in Caenorhabditis elegans using a high density polymorphism map. Nature Genet. 28, 160–164 (2001)

    Article  CAS  Google Scholar 

  12. Lee, R. C., Feinbaum, R. L. & Ambros, V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75, 843–854 (1993)

    Article  CAS  Google Scholar 

  13. Olsen, P. H. & Ambros, V. The lin-4 regulatory RNA controls developmental timing in Caenorhabditis elegans by blocking LIN-14 protein synthesis after the initiation of translation. Dev. Biol. 216, 671–680 (1999)

    Article  CAS  Google Scholar 

  14. Ambros, V., Lee, R. C., Lavanway, A., Williams, P. T. & Jewell, D. MicroRNAs and other tiny endogenous RNAs in C. elegans. Curr. Biol. 13, 807–818 (2003)

    Article  CAS  Google Scholar 

  15. Lim, L. P. et al. The microRNAs of Caenorhabditis elegans. Genes Dev. 17, 991–1008 (2003)

    Article  CAS  Google Scholar 

  16. Grad, Y. et al. Computational and experimental identification of C. elegans microRNAs. Mol. Cell 11, 1253–1263 (2003)

    Article  CAS  Google Scholar 

  17. Lau, N. C., Lim, L. P., Weinstein, E. G. & Bartel, D. P. An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science 294, 858–862 (2001)

    Article  ADS  CAS  Google Scholar 

  18. Johnson, S. M., Lin, S. Y. & Slack, F. J. The time of appearance of the C. elegans let-7 microRNA is transcriptionally controlled utilizing a temporal regulatory element in its promoter. Dev. Biol. 259, 364–379 (2003)

    Article  CAS  Google Scholar 

  19. Lanjuin, A., VanHoven, M. K., Bargmann, C. I., Thompson, J. K. & Sengupta, P. Otx/otd homeobox genes specify distinct sensory neuron identities in C. elegans. Dev. Cell 5, 621–633 (2003)

    Article  CAS  Google Scholar 

  20. Stark, A., Brennecke, J., Russell, R. B. & Cohen, S. M. Identification of Drosphila MicroRNA targets. PLOS Biol. Online publication 13 October 2003 (doi:10.1371/journal.pbio.0000060)

  21. Palmer, R. E., Inoue, T., Sherwood, D. R., Jiang, L. I. & Sternberg, P. W. Caenorhabditis elegans cog-1 locus encodes GTX/Nkx6.1 homeodomain proteins and regulates multiple aspects of reproductive system development. Dev. Biol. 252, 202–213 (2002)

    Article  CAS  Google Scholar 

  22. Hobert, O. PCR fusion-based approach to create reporter gene constructs for expression analysis in transgenic C. elegans. Biotechniques 32, 728–730 (2002)

    Article  CAS  Google Scholar 

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Acknowledgements

We are grateful to A. Wenick and B. Reinhart for suggestions; Q. Chen for technical assistance; R. Mann, L. Johnston, P. Sengupta and A. Lanjuin for critically reading the manuscript; and the NSF (R.J.J.) and NIH (O.H.) for funding.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biophysics, Center for Neurobiology and Behavior, Columbia University, College of Physicians and Surgeons, 701 W.168th Street, New York, New York, 10032, USA

    Robert J. Johnston Jr & Oliver Hobert

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Correspondence to Oliver Hobert.

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The authors declare that they have no competing financial interests.

Supplementary information

41586_2003_BFnature02255_MOESM1_ESM.doc

Supplementary Information: Experimental procedures and quantification of defects described in the figures in the main paper and list of constructs and primers used (DOC 40 kb)

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Johnston, R., Hobert, O. A microRNA controlling left/right neuronal asymmetry in Caenorhabditis elegans. Nature 426, 845–849 (2003). https://doi.org/10.1038/nature02255

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