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Ephrin Reverse Signaling Induces Mouse Palatal Fusion and Epithelial To Mesenchymal Transition In Cultured Medial Edge Epithelia
Author(s) -
Serrano Maria J,
Nawshad Ali,
Ibrahim Isra,
Dyke Jeffrey,
Svoboda Kathy K,
Benson M Douglas
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.963.2
Subject(s) - ephrin , erythropoietin producing hepatocellular (eph) receptor , microbiology and biotechnology , mesenchyme , fusion protein , signal transduction , biology , receptor tyrosine kinase , epithelial–mesenchymal transition , chemistry , mesenchymal stem cell , downregulation and upregulation , recombinant dna , genetics , gene
Understanding the molecular events in palate development is a prerequisite to more effective treatment of cleft palate. The secondary palate in humans and mice forms from shelves of mesenchyme covered with epithelium. These shelves adhere to form the midline epithelial seam (MES). MES cells then proceed through epithelial to mesenchymal transition (EMT) and apoptosis to yield a fused palate. This fusion requires Transforming Growth Factor β3 (Tgfβ3). Eph receptor tyrosine kinases and their ephrin ligands are responsible for many contact‐mediated developmental processes. Binding of ephrins causes receptor activation in Eph‐bearing cells (forward signaling), and intracellular signaling inside ephrin‐bearing cells (reverse signaling). Previously, we established that ephrin‐B reverse signaling is required for palate fusion in mice and is sufficient to cause fusion in chicken palates without Tgfβ3. In this study, we asked if activation of ephrin reverse signaling is sufficient to fuse mouse palatal shelves in vitro in the absence of Tgfβ3. We cultured embryonic day 13.5 mouse palatal shelves with a blocking antibody against Tgfβ3 that prevents fusion and clustered recombinant EphB2/Fc protein. EphB2/Fc treatment restored fusion. We also found that treatment with EphB2/Fc of cultured cells isolated from MES induced phenotypic and gene expression changes indicative of EMT. These results demonstrate that ephrin reverse signaling is sufficient to cause fusion of the mammalian palate. Grant Funding Source : RO3DE020119 (NIDCR)