Disruption of the murine homeobox gene Cdx1 affects axial skeletal identities by altering the mesodermal expression domains of Hox genes

Vasanta Subramanian, Barbara I. Meyer, Peter Gruss

Research output: Contribution to journalArticlepeer-review

Abstract

Cdx1 is expressed along the embryonic axis from day 7.5 postcoitum until day 12, by which time the anterior limit of expression has regressed from the hindbrain level to the forelimb bud region. To assign a functional role for Cdx1 in murine embryonic development, we have inactivated the gene via homologous recombination. Viable fertile homozygous mutant mice were obtained that show anterior homeotic transformations of vertebrae. These abnormalities were concomitant with posterior shifts of Hox gene expression domains in the somitic mesoderm. The presence of putative Cdx1-binding sites in Hox gene control regions as well as in vitro transactivation of Hoxa-7 indicates; a direct regulation.

Original languageEnglish
Pages (from-to)641-653
Number of pages13
JournalCell
Volume83
Issue number4
DOIs
Publication statusPublished - 17 Nov 1995

Funding

We are especially grateful to Ahmed Mansouri for his help in generating the targeted ES cells. We would like to thank Michael Kessel, Peter Thorogood, Mike Akam, Robert Presley, and members of the Gruss lab for critical comments and valuable discussions. We would also like to thank Ralph Altschtiffel for assistance with the illustrations, and the staff of the animal house, Max Planck Institute, Giittingen, and Lesley Moore, Bath University, for help in the generation and care of the mutants. V. S. would like to thank Ravi Acharya, Tony Rees, Kathryn Robson, and Kamal Chowdhury for their encouragemenlt. During a part of this investigation, V. S. was supported by the Max Planck Society and the British Council. B. M. was supported by the Hochschule Sonderprogramm II. Most of the work was supported by the Max Planck Society and the Deutsche Forschungsgeme!inschaft. Additional support was provided by the Human Frontiers Sck?nce Program. V. S. also thanks the Medical Research Council, United Kingdom, for support.

ASJC Scopus subject areas

  • General Biochemistry,Genetics and Molecular Biology
  • Cell Biology
  • Molecular Biology

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