MicroRNAs in limb development

doi:10.1017/CBO9780511541766.007

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 ,

Jason R. Rock and

Brian D. Harfe

Edited by

Krishnarao Appasani

Foreword by

Sidney Altman and

Victor R. Ambros

Show author details

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

Book contents

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

DOI: https://doi.org/10.1017/CBO9780511541766.007 [Opens in a new window]

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.)

Book purchase

Temporarily unavailable

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