Ephrin reverse signaling controls palate fusion via a PI3 kinase-dependent mechanism.
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.
Department of Biomedical Sciences, Texas A&M Health Science Center Baylor College of Dentistry, Dallas, Texas, USA.
Symone
S
San Miguel
Maria J
MJ
Serrano
Ashneet
A
Sachar
Mark
M
Henkemeyer
Kathy K H
KK
Svoboda
M Douglas
MD
Benson
D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D002972:Cleft Palate / Q000209:etiology / Q000503:physiopathology; D036342:Ephrins / Q000235:genetics / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology; D006801:Humans; D051379:Mice; D010159:Palate / Q000166:cytology / Q000196:embryology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D015398:Signal Transduction / Q000502:physiology*; D053782:Transforming Growth Factor beta3 / Q000378:metabolism
D036342:Ephrins; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D053782:Transforming Growth Factor beta3
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