An essential role of Bmp4 in the atrioventricular septation of the mouse heart

  1. Kai Jiao1,3,
  2. Holger Kulessa2,
  3. Kevin Tompkins1,3,
  4. Yingna Zhou2,
  5. Lorene Batts1,3,
  6. H. Scott Baldwin3, and
  7. Brigid L.M. Hogan1,4,5
  1. 1 Howard Hughes Medical Institute, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
  2. 2 Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
  3. 3 Division of Pediatric Cardiology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA

Abstract

Proper septation and valvulogenesis during cardiogenesis depend on interactions between the myocardium and the endocardium. By combining use of a hypomorphic Bone morphogenetic protein 4 (Bmp4) allele with conditional gene inactivation, we here identify Bmp4 as a signal from the myocardium directly mediating atrioventricular septation. Defects in this process cause one of the most common human congenital heart abnormalities, atrioventricular canal defect (AVCD). The spectrum of defects obtained through altering Bmp4 expression in the myocardium recapitulates the range of AVCDs diagnosed in patients, thus providing a useful genetic model with AVCD as the primary defect.

Keywords

Footnotes

  • Article published online ahead of print. Article and publication date are at http://www.genesdev.org/cgi/doi/10.1101/gad.1124803.

  • 4 Present address: Department of Cell Biology, Duke University Medical Center, Box 3709, Durham, NC 27710, USA

  • 5 Corresponding author. E-MAIL b.hogan{at}cellbio.duke.edu; FAX (919) 864-8592.

    • Accepted August 5, 2003.
    • Received June 24, 2003.
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