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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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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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