Cell autonomous requirement of endocardial Smad4 during atrioventricular cushion development in mouse embryos

Authors

  • Langying Song,

    1. Research Division, Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama
    Current affiliation:
    1. Department of Molecular Biosciences, University of California, Davis, CA 95616
    Search for more papers by this author
    • Langying Song and Mei Zhao contributed equally to this work.

  • Mei Zhao,

    1. Research Division, Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama
    Current affiliation:
    1. Department of Cardiology, Shengjing Hospital, China Medical University, Shenyang 110004, P. R. China
    Search for more papers by this author
    • Langying Song and Mei Zhao contributed equally to this work.

  • Bingruo Wu,

    1. Department of Genetics, Albert Einstein College of Medicine, New York, New York
    Search for more papers by this author
  • Bin Zhou,

    1. Department of Genetics, Albert Einstein College of Medicine, New York, New York
    Search for more papers by this author
  • Qin Wang,

    1. Department of Physiology and Biophysics, the University of Alabama at Birmingham, Birmingham, Alabama
    Search for more papers by this author
  • Kai Jiao

    Corresponding author
    1. Research Division, Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama
    • Department of Genetics, University of Alabama at Birmingham, 720 20th St. S., 768 Kaul Building, Birmingham, AL 35294
    Search for more papers by this author

Abstract

Atrioventricular (AV) cushions are the precursors of AV septum and valves. In this study, we examined roles of Smad4 during AV cushion development using a conditional gene inactivation approach. We found that endothelial/endocardial inactivation of Smad4 led to the hypocellular AV cushion defect and that both reduced cell proliferation and increased apoptosis contributed to the defect. Expression of multiple genes critical for cushion development was down-regulated in mutant embryos. In collagen gel assays, the number of mesenchymal cells formed is significantly reduced in mutant AV explants compared to that in control explants, suggesting that the reduction of cushion mesenchyme formation in mutants is unlikely secondary to their gross vasculature abnormalities. Using a previously developed immortal endocardial cell line, we showed that Smad4 is required for BMP signaling- stimulated upregulation of Tbx20 and Gata4. Therefore, our data collectively support the cell-autonomous requirement of endocardial Smad4 in regulating AV cushion development. Developmental Dynamics, 2011. © 2010 Wiley-Liss, Inc.

Ancillary