Ephrin reverse signaling mediates palatal fusion and epithelial-to-mesenchymal transition independently of tgfß3

Autor: M. Douglas Benson, Kathy K.H. Svoboda, Jingpeng Liu, Ali Nawshad, Maria J. Serrano
Rok vydání: 2015
Předmět:
Zdroj: Journal of Cellular Physiology. 230:2961-2972
ISSN: 0021-9541
DOI: 10.1002/jcp.25025
Popis: The mammalian secondary palate forms from shelves of epithelia-covered mesenchyme that meet at midline and fuse. The midline epithelial seam (MES) is thought to degrade by apoptosis, epithelial-to-mesenchymal transition (EMT), or both. Failure to degrade the MES blocks fusion and causes cleft palate. It was previously thought that transforming growth factor s3 (Tgfs3) is required to initiate fusion. Members of the Eph tyrosine kinase receptor family and their membrane-bound ephrin ligands are expressed on the MES. We demonstrated that treatment of mouse palates with recombinant EphB2/Fc to activate ephrin reverse signaling (where the ephrin acts as a receptor and transduces signals from its cytodomain) was sufficient to cause mouse palatal fusion when Tgfs3 signaling was blocked by an antibody against Tgfs3 or by an inhibitor of the TgfsrI serine/threonine receptor kinase. Cultured palatal epithelial cells traded their expression of epithelial cell markers for that of mesenchymal cells and became motile after treatment with EphB2/Fc. They concurrently increased their expression of the EMT-associated transcription factors Snail, Sip1, and Twist1. EphB2/Fc did not cause apoptosis in these cells. These data reveal that ephrin reverse signaling directs palatal fusion in mammals through a mechanism that involves EMT but not apoptosis and activates a gene expression program not previously associated with ephrin reverse signaling.
Databáze: OpenAIRE
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