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MicroRNA-responsive 'sensor' transgenes uncover Hox-like and other developmentally regulated patterns of vertebrate microRNA expression

Nature Genetics volume 36, pages 1079–1083 (2004)Cite this article

A Corrigendum to this article was published on 01 November 2004

Abstract

MicroRNAs (miRNAs) are a class of short (∼22-nt) noncoding RNA molecules that downregulate expression of their mRNA targets. Since their discovery as regulators of developmental timing in Caenorhabditis elegans, hundreds of miRNAs have been identified in both animals and plants1. Here, we report a technique for visualizing detailed miRNA expression patterns in mouse embryos. We elucidate the tissue-specific expression of several miRNAs during embryogenesis, including two encoded by genes embedded in homeobox (Hox) clusters, miR-10a and miR-196a. These two miRNAs are expressed in patterns that are markedly reminiscent of those of Hox genes. Furthermore, miR-196a negatively regulates Hoxb8, indicating that its restricted expression pattern probably reflects a role in the patterning function of the Hox complex.

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Figure 1: Transgenic sensor design.
Figure 2: Patterns of miR-let-7 expression in transgenic embryos.
Figure 3: miR-1 is expressed in the heart.
Figure 4: Two families of miRNAs, miR-10 and miR-196, are embedded in the mouse Hox clusters.
Figure 5: miR-10a and miR-196a are expressed in Hox-like patterns.
Figure 6: miR-196a downregulates Hoxb8 by mediating RNA cleavage.

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Acknowledgements

We thank S. Dymecki for plasmids; A. Abney and L. Du for pronuclear injections of the transgenes; members of the laboratories of C.J.T., C. Cepko, S. Dymecki and P.A.S. for discussions and advice; and A. Brent for critical reading of the manuscript. This work was supported by a grant from the March of Dimes to C.J.T., and by a US National Institutes of Health MERIT award and grants from the National Cancer Institute to P.A.S. J.H.M. and M.T.M. are supported by postdoctoral fellowships from the National Institutes of Health and the Cancer Research Institute, respectively.

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Author notes

  1. Amy E Pasquinelli

    Present address: Department of Molecular Biology, University of California, San Diego, La Jolla, California, 92093, USA

  2. Michael T McManus

    Present address: Department of Microbiology and Immunology, Diabetes Center, University of California, San Francisco, San Francisco, California, 94143, USA

Authors and Affiliations

  1. Department of Genetics, Harvard Medical School, Boston, 02115, Massachusetts, USA

    Jennifer H Mansfield, Amy E Pasquinelli, Gary Ruvkun & Clifford J Tabin

  2. Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainsville, 32610, Florida, USA

    Brian D Harfe

  3. Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, 02139, Massachusetts, USA

    Brian D Harfe, John Obenauer, Aadel Chaudhuri, Raphael Farzan-Kashani, Phillip A Sharp & Michael T McManus

  4. St. Jude Children's Research Hospital, Memphis, 38105, Tennessee, USA

    Robert Nissen

  5. Department of Computer Sciences, Rensselaer Polytechnic Institute, Troy, 12180, New York, USA

    Jalagani Srineel

  6. Department of Mathematical Sciences, Rensselaer Polytechnic Institute, Troy, 12180, New York, USA

    Michael Zuker

  7. Department of Molecular Biology, Massachusetts General Hospital, Boston, 02114, Massachusetts, USA

    Amy E Pasquinelli & Gary Ruvkun

  8. Department of Biology, McGovern Institute, Massachusetts Institute of Technology, Cambridge, 02139, Massachusetts, USA

    Phillip A Sharp

  9. Department of Molecular Biology, University of California, San Diego, La Jolla, California, 92093, USA

    Michael T McManus

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Correspondence to Clifford J Tabin or Michael T McManus.

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The authors declare no competing financial interests.

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Mansfield, J., Harfe, B., Nissen, R. et al. MicroRNA-responsive 'sensor' transgenes uncover Hox-like and other developmentally regulated patterns of vertebrate microRNA expression. Nat Genet 36, 1079–1083 (2004). https://doi.org/10.1038/ng1421

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