Ephrin reverse signaling controls palate fusion via a PI3 kinase-dependent mechanism

Authors

  • Symone San Miguel,

    1. Department of Biomedical Sciences, Texas A&M Health Science Center Baylor College of Dentistry, Dallas, Texas
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    • Symone San Miguel and Maria J. Serrano contributed equally to this study.

  • Maria J. Serrano,

    1. Department of Biomedical Sciences, Texas A&M Health Science Center Baylor College of Dentistry, Dallas, Texas
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    • Symone San Miguel and Maria J. Serrano contributed equally to this study.

  • Ashneet Sachar,

    1. Department of Biomedical Sciences, Texas A&M Health Science Center Baylor College of Dentistry, Dallas, Texas
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  • Mark Henkemeyer,

    1. Department of Developmental Biology, University of Texas Southwestern Medical Center, Dallas, Texas
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  • Kathy K. H. Svoboda,

    1. Department of Biomedical Sciences, Texas A&M Health Science Center Baylor College of Dentistry, Dallas, Texas
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  • M. Douglas Benson

    Corresponding author
    1. Department of Biomedical Sciences, Texas A&M Health Science Center Baylor College of Dentistry, Dallas, Texas
    • Department of Biomedical Sciences, Texas A&M Health Science Center Baylor College of Dentistry, 3302 Gaston Ave., Dallas, TX 75246
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Abstract

Secondary palate fusion requires adhesion and epithelial-to-mesenchymal transition (EMT) of the epithelial layers on opposing palatal shelves. This EMT requires transforming growth factor β3 (TGFβ3), and its failure results in cleft palate. Ephrins, and their receptors, the Ephs, are responsible for migration, adhesion, and midline closure events throughout development. Ephrins can also act as signal-transducing receptors in these processes, with the Ephs serving as ligands (termed “reverse” signaling). We found that activation of ephrin reverse signaling in chicken palates induced fusion in the absence of TGFβ3, and that PI3K inhibition abrogated this effect. Further, blockage of reverse signaling inhibited TGFβ3-induced fusion in the chicken and natural fusion in the mouse. Thus, ephrin reverse signaling is necessary and sufficient to induce palate fusion independent of TGFβ3. These data describe both a novel role for ephrins in palate morphogenesis, and a previously unknown mechanism of ephrin signaling. Developmental Dynamics 240:357–364, 2011. © 2011 Wiley-Liss, Inc.

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