Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 11 June 2004:
Vol. 304. no. 5677, pp. 1669 - 1672
DOI: 10.1126/science.1096049
Prev | Table of Contents | Next

Reports

A Dual Role for Hox Genes in Limb Anterior-Posterior Asymmetry

József Zákány, Marie Kmita, Denis Duboule*

Anterior-to-posterior patterning, the process whereby our digits are differently shaped, is a key aspect of limb development. It depends on the localized expression in posterior limb bud of Sonic hedgehog (Shh) and the morphogenetic potential of its diffusing product. By using an inversion of and a large deficiency in the mouse HoxD cluster, we found that a perturbation in the early collinear expression of Hoxd11, Hoxd12, and Hoxd13 in limb buds led to a loss of asymmetry. Ectopic Hox gene expression triggered abnormal Shh transcription, which in turn induced symmetrical expression of Hox genes in digits, thereby generating double posterior limbs. We conclude that early posterior restriction of Hox gene products sets up an anterior-posterior prepattern, which determines the localized activation of Shh. This signal is subsequently translated into digit morphological asymmetry by promoting the late expression of Hoxd genes, two collinear processes relying on opposite genomic topographies, upstream and downstream Shh signaling.

Department of Zoology and Animal Biology and National Program Frontiers in Genetics, University of Geneva, Sciences III, Quai Ernest Ansermet 30, 1211 Geneva 4, Switzerland.

* To whom correspondence should be addressed. E-mail: Denis.Duboule{at}zoo.unige.ch

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Cholesterol Metabolism: the Main Pathway Acting Downstream of Cytochrome P450 Oxidoreductase in Skeletal Development of the Limb.
K. Schmidt, C. Hughes, J. A. Chudek, S. R. Goodyear, R. M. Aspden, R. Talbot, T. E. Gundersen, R. Blomhoff, C. Henderson, C. R. Wolf, et al. (2009)
Mol. Cell. Biol. 29, 2716-2729
   Abstract »    Full Text »    PDF »
Shared developmental mechanisms pattern the vertebrate gill arch and paired fin skeletons.
J. A. Gillis, R. D. Dahn, and N. H. Shubin (2009)
PNAS 106, 5720-5724
   Abstract »    Full Text »    PDF »
Adaptive Evolution of 5'HoxD Genes in the Origin and Diversification of the Cetacean Flipper.
Z. Wang, L. Yuan, S. J. Rossiter, X. Zuo, B. Ru, H. Zhong, N. Han, G. Jones, P. D. Jepson, and S. Zhang (2009)
Mol. Biol. Evol. 26, 613-622
   Abstract »    Full Text »    PDF »
Inducing Segmental Aneuploid Mosaicism in the Mouse Through Targeted Asymmetric Sister Chromatid Event of Recombination.
A. Duchon, V. Besson, P. L. Pereira, L. Magnol, and Y. Herault (2008)
Genetics 180, 51-59
   Abstract »    Full Text »    PDF »
Uncoupling the Role of Sonic Hedgehog in Limb Development: Growth and Specification.
P. Francis-West and R. Hill (2008)
Science Signaling 1, pe34
   Abstract »    Full Text »    PDF »
Dickkopf 1 (DKK1) regulates skin pigmentation and thickness by affecting Wnt/{beta}-catenin signaling in keratinocytes.
Y. Yamaguchi, T. Passeron, T. Hoashi, H. Watabe, F. Rouzaud, K.-i. Yasumoto, T. Hara, C. Tohyama, I. Katayama, T. Miki, et al. (2008)
FASEB J 22, 1009-1020
   Abstract »    Full Text »    PDF »
Ectopic nuclear reorganisation driven by a Hoxb1 transgene transposed into Hoxd.
C. Morey, N. R. Da Silva, M. Kmita, D. Duboule, and W. A. Bickmore (2008)
J. Cell Sci. 121, 571-577
   Abstract »    Full Text »    PDF »
Tailored Hox gene transcription and the making of the thumb.
J. Deschamps (2008)
Genes & Dev. 22, 293-296
   Full Text »    PDF »
Modeling Hox gene regulation in digits: reverse collinearity and the molecular origin of thumbness.
T. Montavon, J.-F. Le Garrec, M. Kerszberg, and D. Duboule (2008)
Genes & Dev. 22, 346-359
   Abstract »    Full Text »    PDF »
Hox gene function in vertebrate gut morphogenesis: the case of the caecum.
G. Zacchetti, D. Duboule, and J. Zakany (2007)
Development 134, 3967-3973
   Abstract »    Full Text »    PDF »
The molecular basis of Pallister Hall associated polydactyly.
P. Hill, B. Wang, and U. Ruther (2007)
Hum. Mol. Genet. 16, 2089-2096
   Abstract »    Full Text »    PDF »
Nuclear reorganisation and chromatin decondensation are conserved, but distinct, mechanisms linked to Hox gene activation.
C. Morey, N. R. Da Silva, P. Perry, and W. A. Bickmore (2007)
Development 134, 909-919
   Abstract »    Full Text »    PDF »
Differential regulation of gene expression in the digit forming area of the mouse limb bud by SHH and gremlin 1/FGF-mediated epithelial-mesenchymal signalling.
L. Panman, A. Galli, N. Lagarde, O. Michos, G. Soete, A. Zuniga, and R. Zeller (2006)
Development 133, 3419-3428
   Abstract »    Full Text »    PDF »
Pbx1/Pbx2 requirement for distal limb patterning is mediated by the hierarchical control of Hox gene spatial distribution and Shh expression.
T. D. Capellini, G. Di Giacomo, V. Salsi, A. Brendolan, E. Ferretti, D. Srivastava, V. Zappavigna, and L. Selleri (2006)
Development 133, 2263-2273
   Abstract »    Full Text »    PDF »
Developmental basis for hind-limb loss in dolphins and origin of the cetacean bodyplan.
J. G. M. Thewissen, M. J. Cohn, L. S. Stevens, S. Bajpai, J. Heyning, and W. E. Horton Jr. (2006)
PNAS 103, 8414-8418
   Abstract »    Full Text »    PDF »
Highly conserved syntenic blocks at the vertebrate Hox loci and conserved regulatory elements within and outside Hox gene clusters.
A. P. Lee, E. G. L. Koh, A. Tay, S. Brenner, and B. Venkatesh (2006)
PNAS 103, 6994-6999
   Abstract »    Full Text »    PDF »
Breakpoints around the HOXD cluster result in various limb malformations.
B Dlugaszewska, A Silahtaroglu, C Menzel, S Kubart, M Cohen, S Mundlos, Z Tumer, K Kjaer, U Friedrich, H-H Ropers, et al. (2006)
J. Med. Genet. 43, 111-118
   Abstract »    Full Text »    PDF »
FGFR1 function at the earliest stages of mouse limb development plays an indispensable role in subsequent autopod morphogenesis.
C. Li, X. Xu, D. K. Nelson, T. Williams, M. R. Kuehn, and C.-X. Deng (2005)
Development 132, 4755-4764
   Abstract »    Full Text »    PDF »
Cooperative requirement of the Gli proteins in neurogenesis.
V. Nguyen, A. L. Chokas, B. Stecca, and A. R. i Altaba (2005)
Development 132, 3267-3279
   Abstract »    Full Text »    PDF »
Developmental regulation of the Hox genes during axial morphogenesis in the mouse.
J. Deschamps and J. van Nes (2005)
Development 132, 2931-2942
   Abstract »    Full Text »    PDF »
Comparative analysis of genes downstream of the Hoxd cluster in developing digits and external genitalia.
J. Cobb and D. Duboule (2005)
Development 132, 3055-3067
   Abstract »    Full Text »    PDF »
Hox-controlled reorganisation of intrasegmental patterning cues underlies Drosophila posterior spiracle organogenesis.
S. Merabet, J. C.-G. Hombria, N. Hu, J. Pradel, and Y. Graba (2005)
Development 132, 3093-3102
   Abstract »    Full Text »    PDF »
Identification of coexpressed gene clusters in a comparative analysis of transcriptome and proteome in mouse tissues.
T. Mijalski, A. Harder, T. Halder, M. Kersten, M. Horsch, T. M. Strom, H. V. Liebscher, F. Lottspeich, M. H. de Angelis, and J. Beckers (2005)
PNAS 102, 8621-8626
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)