Skip to main content Accessibility help
×
Hostname: page-component-77c89778f8-gq7q9 Total loading time: 0 Render date: 2024-07-18T19:34:38.009Z Has data issue: false hasContentIssue false

4 - MicroRNAs in limb development

from I - Discovery of microRNAs in various organisms

Published online by Cambridge University Press:  22 August 2009

Danielle M. Maatouk
Affiliation:
Department of Molecular Genetics & Microbiology, University of Florida College of Medicine 1600 SW Archer Road Gainesville, FL 32610-0266 USA
Jason R. Rock
Affiliation:
Department of Molecular Genetics & Microbiology, University of Florida College of Medicine 1600 SW Archer Road Gainesville, FL 32610-0266 USA
Brian D. Harfe
Affiliation:
Department of Molecular Genetics & Microbiology, University of Florida College of Medicine 1600 SW Archer Road Gainesville, FL 32610-0266 USA
Get access

Summary

Introduction

The vertebrate limb is a highly organized structure that must be patterned along three axes during development: anteroposterior, dorsoventral, and proximodistal (Tickle, 2003). For decades, the limb has served as a choice model system for developmental biologists because of the ease with which it can be manipulated and an organism's ability to survive with abnormal or absent limbs. Despite years of intense investigation, many of the molecules responsible for limb pattern formation are still not known.

Recently, a class of non-coding RNAs, the microRNAs (miRNAs), have been implicated in limb development. These molecules are ~22 nt in their mature form and can bind to mRNAs, leading to their degradation or inhibition of protein production (McManus and Sharp, 2002). The first miRNA to be discovered, lin-4, was identified in a forward genetic screen aimed at identifying developmental timing defects in C. elegans (Lee et al., 1993). Nearly a decade after the discovery of lin-4 in nematodes, a second miRNA, let-7, was identified in organisms ranging from C. elegans to humans (Pasquinelli et al., 2000; Reinhart et al., 2000). In the years since, at least 326 miRNAs have been validated in humans and 249 in mouse (Griffiths-Jones, 2004). Only a few of these miRNAs have known functions (reviewed in Harfe (2005)). Our lab is interested in the role miRNAs play in patterning the vertebrate limb.

MicroRNA processing

Mature miRNAs are produced through two cleavage events by members of the RNaseIII family of nucleases (Bernstein et al., 2001; Hutvagner et al., 2001; Ketting et al., 2001; Lee et al. 2003).

Type
Chapter
Information
MicroRNAs
From Basic Science to Disease Biology
, pp. 58 - 69
Publisher: Cambridge University Press
Print publication year: 2007

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Bagga, S., Bracht, J., Hunter, S.et al. (2005). Regulation by let-7 and lin-4 miRNAs results in target mRNA degradation. Cell, 122, 553–563.Google Scholar
Bateson, W. (1894). Materials for the Study of Variation. New York: Macmillan.
Bernstein, E., Caudy, A. A., Hammond, S. M. and Hannon, G. J. (2001). Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature, 409, 363–366.Google Scholar
Bernstein, E., Kim, S. Y., Carmell, M. A.et al. (2003). Dicer is essential for mouse development. Nature Genetics, 35, 215–217.Google Scholar
Boncinelli, E., Simeone, A., Acampora, D. and Mavilio, F. (1991). HOX gene activation by retinoic acid. Trends in Genetics, 7, 329–334.Google Scholar
Brennecke, J., Hipfner, D. R., Stark, A., Russell, R. B. and Cohen, S. M. (2003). Bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila. Cell, 113, 25–36.Google Scholar
Charite, J., Graaff, W., Shen, S. and Deschamps, J. (1994). Ectopic expression of Hoxb-8 causes duplication of the ZPA in the forelimb and homeotic transformation of axial structures. Cell, 78, 589–601.Google Scholar
Dolle, P. and Duboule, D. (1989). Two gene members of the murine HOX-5 complex show regional and cell-type specific expression in developing limbs and gonads. European Molecular Biology Organization Journal, 8, 1507–1515.Google Scholar
Dolle, P., Izpisua-Belmonte, J. C., Falkenstein, H., Renucci, A. and Duboule, D. (1989). Coordinate expression of the murine Hox-5 complex homoeobox-containing genes during limb pattern formation. Nature, 342, 767–772.Google Scholar
Duboule, D. and Dolle, P. (1989). The structural and functional organization of the murine HOX gene family resembles that of Drosophila homeotic genes. European Molecular Biology Organization Journal, 8, 1497–1505.Google Scholar
Graham, A., Papalopulu, N. and Krumlauf, R. (1989). The murine and Drosophila homeobox gene complexes have common features of organization and expression. Cell, 57, 367–378.Google Scholar
Griffiths-Jones, S. (2004). The microRNA registry. Nucleic Acids Research, 32, D109–D111.Google Scholar
Grishok, A., Pasquinelli, A. E., Conte, D.et al. (2001). Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C. elegans developmental timing. Cell, 106, 23–34.Google Scholar
Harfe, B. D. (2005). MicroRNAs in vertebrate development. Current Opinion in Genetics & Development, 15, 410–415.Google Scholar
Harfe, B. D., Scherz, P. J., Nissim, S.et al. (2004). Evidence for an expansion-based temporal Shh gradient in specifying vertebrate digit identities. Cell, 118, 517–528.Google Scholar
Harfe, B. D., McManus, M. T., Mansfield, J. H., Hornstein, E. and Tabin, C. J. (2005). The RNaseIII enzyme Dicer is required for morphogenesis but not patterning of the vertebrate limb. Proceedings of the National Academy of Sciences USA, 102, 10 898–10 903.Google Scholar
Harris, K. S., Zhang, Z., McManus, M. T., Harfe, B. D. and Sun, X. (2006). Dicer function is essential for lung epithelium morphogenesis. Proceedings of the National Academy of Sciences USA (in press).
Hornstein, E., Mansfield, J. H., Yekta, S.et al. (2005). The microRNA miR-196 acts upstream of Hoxb8 and Shh in limb development. Nature, 438, 671–674.Google Scholar
Hutvagner, G., McLachlan, J., Pasquinelli, A. E.et al. (2001). A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA. Science, 293, 834–838.Google Scholar
Izpisua-Belmonte, J. C., Falkenstein, H., Dolle, P., Renucci, A. and Duboule, D. (1991). Murine genes related to the Drosophila AbdB homeotic genes are sequentially expressed during development of the posterior part of the body. European Molecular Biology Organization Journal, 10, 2279–2289.Google Scholar
Jakymiw, A., Lian, S., Eystathioy, T.et al. (2005). Disruption of GW bodies impairs mammalian RNA interference. Nature Cell Biology, 7, 1167–1174.Google Scholar
Ketting, R. F., Fischer, S. E., Bernstein, E.et al. (2001). Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C. elegans. Genes & Development, 15, 2654–2659.Google Scholar
Kos, C. H. (2004). Cre/loxP system for generating tissue-specific knockout mouse models. Nutrition Reviews, 62, 243–246.Google Scholar
Krumlauf, R. (1994). Hox genes in vertebrate development. Cell, 78, 191–201.Google Scholar
Lagos-Quintana, M., Rauhut, R., Meyer, J., Borkhardt, A. and Tuschl, T. (2003). New microRNAs from mouse and human. RNA, 9, 175–179.Google Scholar
Lee, R. C., Feinbaum, R. L. and Ambros, V. (1993). The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell, 75, 843–854.Google Scholar
Lee, Y., Ahn, C., Han, J.et al. (2003). The nuclear RNase III Drosha initiates microRNA processing. Nature, 425, 415–419.Google Scholar
Lewis, B. P., Shih, I. H., Jones-Rhoades, M. W., Bartel, D. P. and Burge, C. B. (2003). Prediction of mammalian microRNA targets. Cell, 115, 787–98.Google Scholar
Lewis, B. P., Burge, C. B. and Bartel, D. P. (2005). Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell, 120, 15–20.Google Scholar
Lewis, E. B. (1978). A gene complex controlling segmentation in Drosophila. Nature, 276, 565–570.Google Scholar
Lim, L. P., Glasner, M. E., Yekta, S., Burge, C. B. and Bartel, D. P. (2003). Vertebrate microRNA genes. Science, 299, 1540.Google Scholar
Lingel, A., Simon, B., Izaurralde, E. and Sattler, M. (2003). Structure and nucleic-acid binding of the Drosophila Argonaute 2 PAZ domain. Nature, 426, 465–469.Google Scholar
Liu, J., Valencia-Sanchez, M. A., Hannon, G. J. and Parker, R. (2005). MicroRNA-dependent localization of targeted mRNAs to mammalian P-bodies. Nature Cell Biology, 7, 719–723.Google Scholar
Logan, M., Martin, J. F., Nagy, A.et al. (2002). Expression of Cre Recombinase in the developing mouse limb bud driven by a Prxl enhancer. Genesis, 33, 77–80.Google Scholar
Lu, H. C., Revelli, J. P., Goering, L., Thaller, C. and Eichele, G. (1997). Retinoid signaling is required for the establishment of a ZPA and for the expression of Hoxb-8, a mediator of ZPA formation. Development, 124, 1643–1651.Google Scholar
Lund, E., Guttinger, S., Calado, A., Dahlberg, J. E. and Kutay, U. (2004). Nuclear export of microRNA precursors. Science, 303, 95–98.Google Scholar
Mansfield, J. H., Harfe, B. D., Nissen, R.et al. (2004). MicroRNA-responsive ‘sensor’ transgenes uncover Hox-like and other developmentally regulated patterns of vertebrate microRNA expression. Nature Genetics, 36, 1079–1083.Google Scholar
Martin, P. (1990). Tissue patterning in the developing mouse limb. International Journal of Developmental Biology, 34, 323–336.Google Scholar
McGinnis, W. and Krumlauf, R. (1992). Homeobox genes and axial patterning. Cell, 68, 283–302.Google Scholar
McGinnis, W., Levine, M. S., Hafen, E., Kuroiwa, A. and Gehring, W. J. (1984). A conserved DNA sequence in homoeotic genes of the Drosophila Antennapedia and bithorax complexes. Nature, 308, 428–433.Google Scholar
McManus, M. T. and Sharp, P. A. (2002). Gene silencing in mammals by small interfering RNAs. Nature Reviews Genetics, 3, 737–747.Google Scholar
Min, W., Woo, H. J., Lee, C. S.et al. (1998). 307-bp fragment in HOXA7 upstream sequence is sufficient for anterior boundary formation. DNA and Cell Biology, 17, 293–299.Google Scholar
Murchison, E. P. and Hannon, G. J. (2004). miRNAs on the move: miRNA biogenesis and the RNAi machinery. Current Opinion in Cell Biology, 16, 223–229.Google Scholar
Nelson, C. E., Morgan, B. A., Burke, A. C.et al. (1996). Analysis of Hox gene expression in the chick limb bud. Development, 122, 1449–1466.Google Scholar
Nicholson, R. H. and Nicholson, A. W. (2002). Molecular characterization of a mouse cDNA encoding Dicer, a ribonuclease III ortholog involved in RNA interference. Mammalian Genome, 13, 67–73.Google Scholar
Pasquinelli, A. E., Reinhart, B. J., Slack, F.et al. (2000). Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA. Nature, 408, 86–89.Google Scholar
Reinhart, B. J., Slack, F. J., Basson, M.et al. (2000). The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature, 403, 901–906.Google Scholar
Schwer, B. (2001). A new twist on RNA helicases: DExH/D box proteins as RNPases. Nature Structural Biology, 8, 113–116.Google Scholar
Scott, M. P. (1992). Vertebrate homeobox gene nomenclature. Cell, 71, 551–553.Google Scholar
Scott, M. P. and Weiner, A. J. (1984). Structural relationships among genes that control development: sequence homology between the Antennapedia, Ultrabithorax, and fushi tarazu loci of Drosophila. Proceedings of the National Academy of Sciences USA, 81, 4115–4119.Google Scholar
Song, J. J., Liu, J., Tolia, N. H.et al. (2003). The crystal structure of the Argonaute2 PAZ domain reveals an RNA binding motif in RNAi effector complexes. Nature Structural Biology, 10, 1026–1032.Google Scholar
Stratford, T. H., Kostakopoulou, K. and Maden, M. (1997). Hoxb-8 has a role in establishing early anterior–posterior polarity in chick forelimb but not hindlimb. Development, 124, 4225–4234.Google Scholar
Tickle, C. (2003). Patterning systems – from one end of the limb to the other. Developmental Cell, 4, 449–458.Google Scholar
Akker, E., Fromental-Ramain, C., Graaff, W.et al. (2001). Axial skeletal patterning in mice lacking all paralogous group 8 Hox genes. Development, 128, 1911–1921.Google Scholar
Yan, K. S., Yan, S., Farooq, A.et al. (2003). Structure and conserved RNA binding of the PAZ domain. Nature, 426, 468–474.Google Scholar
Yekta, S., Shih, I. H. and Bartel, D. P. (2004). MicroRNA-directed cleavage of HOXB8 mRNA. Science, 304, 594–596.Google Scholar
Yi, R., Qin, Y., Macara, I. G. and Cullen, B. R. (2003). Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. Genes & Development, 17, 3011–3016.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

  • MicroRNAs in limb development
    • By Danielle M. Maatouk, Department of Molecular Genetics & Microbiology, University of Florida College of Medicine 1600 SW Archer Road Gainesville, FL 32610-0266 USA, Jason R. Rock, Department of Molecular Genetics & Microbiology, University of Florida College of Medicine 1600 SW Archer Road Gainesville, FL 32610-0266 USA, Brian D. Harfe, Department of Molecular Genetics & Microbiology, University of Florida College of Medicine 1600 SW Archer Road Gainesville, FL 32610-0266 USA
  • Edited by Krishnarao Appasani
  • Foreword by Sidney Altman, Victor R. Ambros
  • Book: MicroRNAs
  • Online publication: 22 August 2009
  • Chapter DOI: https://doi.org/10.1017/CBO9780511541766.007
Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

  • MicroRNAs in limb development
    • By Danielle M. Maatouk, Department of Molecular Genetics & Microbiology, University of Florida College of Medicine 1600 SW Archer Road Gainesville, FL 32610-0266 USA, Jason R. Rock, Department of Molecular Genetics & Microbiology, University of Florida College of Medicine 1600 SW Archer Road Gainesville, FL 32610-0266 USA, Brian D. Harfe, Department of Molecular Genetics & Microbiology, University of Florida College of Medicine 1600 SW Archer Road Gainesville, FL 32610-0266 USA
  • Edited by Krishnarao Appasani
  • Foreword by Sidney Altman, Victor R. Ambros
  • Book: MicroRNAs
  • Online publication: 22 August 2009
  • Chapter DOI: https://doi.org/10.1017/CBO9780511541766.007
Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

  • MicroRNAs in limb development
    • By Danielle M. Maatouk, Department of Molecular Genetics & Microbiology, University of Florida College of Medicine 1600 SW Archer Road Gainesville, FL 32610-0266 USA, Jason R. Rock, Department of Molecular Genetics & Microbiology, University of Florida College of Medicine 1600 SW Archer Road Gainesville, FL 32610-0266 USA, Brian D. Harfe, Department of Molecular Genetics & Microbiology, University of Florida College of Medicine 1600 SW Archer Road Gainesville, FL 32610-0266 USA
  • Edited by Krishnarao Appasani
  • Foreword by Sidney Altman, Victor R. Ambros
  • Book: MicroRNAs
  • Online publication: 22 August 2009
  • Chapter DOI: https://doi.org/10.1017/CBO9780511541766.007
Available formats
×