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

Maria J. Serrano, Jingpeng Liu, Kathy K H Svoboda, Ali Nawshad, M. Douglas Benson

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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 ß3 (Tgfß3) 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 Tgfß3 signaling was blocked by an antibody against Tgfß3 or by an inhibitor of the TgfßrI 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.

Original languageEnglish (US)
Pages (from-to)2961-2972
Number of pages12
JournalJournal of Cellular Physiology
Volume230
Issue number12
DOIs
StatePublished - Dec 1 2015

Fingerprint

Ephrins
Epithelial-Mesenchymal Transition
Fusion reactions
Transforming Growth Factors
Palate
Apoptosis
Epithelial Cells
Eph Family Receptors
Mammals
Protein-Serine-Threonine Kinases
Cleft Palate
Mesoderm
Electric fuses
Threonine
Gene expression
Serine
Transcription Factors
Phosphotransferases
Epithelium
Ligands

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Ephrin reverse signaling mediates palatal fusion and epithelial-to-mesenchymal transition independently of tgfß3. / Serrano, Maria J.; Liu, Jingpeng; Svoboda, Kathy K H; Nawshad, Ali; Benson, M. Douglas.

In: Journal of Cellular Physiology, Vol. 230, No. 12, 01.12.2015, p. 2961-2972.

Research output: Contribution to journalArticle

Serrano, Maria J. ; Liu, Jingpeng ; Svoboda, Kathy K H ; Nawshad, Ali ; Benson, M. Douglas. / Ephrin reverse signaling mediates palatal fusion and epithelial-to-mesenchymal transition independently of tgfß3. In: Journal of Cellular Physiology. 2015 ; Vol. 230, No. 12. pp. 2961-2972.
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