Ephrin reverse signaling controls palate fusion via a PI3 kinase-dependent mechanism

Symone San Miguel, Maria J. Serrano, Ashneet Sachar, Mark Henkemeyer, Kathy K H Svoboda, M. Douglas Benson

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)357-364
Number of pages8
JournalDevelopmental Dynamics
Volume240
Issue number2
DOIs
StatePublished - Feb 2011

Fingerprint

Ephrins
Palate
Phosphatidylinositol 3-Kinases
Transforming Growth Factors
Epithelial-Mesenchymal Transition
Chickens
Eph Family Receptors
Cleft Palate
Morphogenesis
Ligands

Keywords

  • Chicken
  • Eph
  • Ephrin
  • Epithelium
  • Mouse
  • Palate
  • PI3 kinase

ASJC Scopus subject areas

  • Developmental Biology

Cite this

San Miguel, S., Serrano, M. J., Sachar, A., Henkemeyer, M., Svoboda, K. K. H., & Benson, M. D. (2011). Ephrin reverse signaling controls palate fusion via a PI3 kinase-dependent mechanism. Developmental Dynamics, 240(2), 357-364. https://doi.org/10.1002/dvdy.22546

Ephrin reverse signaling controls palate fusion via a PI3 kinase-dependent mechanism. / San Miguel, Symone; Serrano, Maria J.; Sachar, Ashneet; Henkemeyer, Mark; Svoboda, Kathy K H; Benson, M. Douglas.

In: Developmental Dynamics, Vol. 240, No. 2, 02.2011, p. 357-364.

Research output: Contribution to journalArticle

San Miguel, S, Serrano, MJ, Sachar, A, Henkemeyer, M, Svoboda, KKH & Benson, MD 2011, 'Ephrin reverse signaling controls palate fusion via a PI3 kinase-dependent mechanism', Developmental Dynamics, vol. 240, no. 2, pp. 357-364. https://doi.org/10.1002/dvdy.22546
San Miguel, Symone ; Serrano, Maria J. ; Sachar, Ashneet ; Henkemeyer, Mark ; Svoboda, Kathy K H ; Benson, M. Douglas. / Ephrin reverse signaling controls palate fusion via a PI3 kinase-dependent mechanism. In: Developmental Dynamics. 2011 ; Vol. 240, No. 2. pp. 357-364.
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