Large scale transgenic and cluster deletion analysis of the HoxD complex separate an ancestral regulatory module from evolutionary innovations

  1. François Spitz1,
  2. Federico Gonzalez1,
  3. Catherine Peichel2,3,
  4. Thomas F. Vogt2,4,
  5. Denis Duboule1,5, and
  6. József Zákány1
  1. 1Department of Zoology and Animal Biology, University of Geneva, Sciences III, 1211 Geneva 4, Switzerland; 2Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA

Abstract

The ancestral role of the Hox gene family is specifying morphogenetic differences along the main body axis. In vertebrates,HoxD genes were also co-opted along with the emergence of novel structures such as limbs and genitalia. We propose that these functional recruitments relied on the appearance, or implementation, of regulatory sequences outside of the complex. Whereas transgenic human and murine HOXD clusters could function during axial patterning, in mice they were not expressed outside the trunk. Accordingly, deletion of the entire cluster abolished axial expression, whereas recently acquired regulatory controls were preserved.

Keywords

Footnotes

  • Present addresses: 3Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA; 4Department of Pharmacology, Merck Research Laboratories, Merck & Co., West Point, PA 19486, USA.

  • 5 Corresponding author.

  • E-MAIL Denis.Duboule{at}zoo.unige.ch; FAX 41-22-702-6795.

  • Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.205701.

    • Received April 12, 2001.
    • Accepted July 2, 2001.
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