Ephrin reverse signaling controls palate fusion via a PI3 kinase-dependent mechanism. Academic Article uri icon


  • 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 3 (TGF3), 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 TGF3, and that PI3K inhibition abrogated this effect. Further, blockage of reverse signaling inhibited TGF3-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 TGF3. These data describe both a novel role for ephrins in palate morphogenesis, and a previously unknown mechanism of ephrin signaling.

published proceedings

  • Dev Dyn

author list (cited authors)

  • San Miguel, S., Serrano, M. J., Sachar, A., Henkemeyer, M., Svoboda, K., & Benson, M. D.

citation count

  • 24

complete list of authors

  • San Miguel, Symone||Serrano, Maria J||Sachar, Ashneet||Henkemeyer, Mark||Svoboda, Kathy KH||Benson, M Douglas

publication date

  • January 2011