Epidermal Growth Factor Impairs Palatal Shelf Adhesion and Fusion in the <b><i>Tgf-β</i></b>₃ Null Mutant

• DOI: 10.1159/000362227
• Publication Date: 2014-12-11T08:27:21Z
• Authors: M. Carmen Barrio; Aurora Del Río; Jorge Murillo; Estela Maldonado; Yamila López-Gord...; Irene Paradas-Lara; Luzmarina Hernandes; Javier Catón; Concepción Martín...
• Keywords: Cleft Palate; MSX1 Transcription Factor; Mice, Inbred C57BL; Mice, Knockout; Mice; 0303 health sciences; 03 medical and health sciences; Transforming Growth Factor beta3; Transforming Growth Factor beta; Animals; Gene Expression Regulation, Developmental; Immunohistochemistry

The cleft palate presented by transforming growth factor-β3 <i>(Tgf-β</i>_<i>3</i><i>)</i> null mutant mice is caused by altered palatal shelf adhesion, cell proliferation, epithelial-to-mesenchymal transformation and cell death. The expression of epidermal growth factor (EGF), transforming growth factor-β1 <i>(Tgf-β</i>_<i>1</i><i>)</i> and muscle segment homeobox-1 <i>(Msx-1)</i> is modified in the palates of these knockout mice, and the cell proliferation defect is caused by the change in EGF expression. In this study, we aimed to determine whether this change in EGF expression has any effect on the other mechanisms altered in <i>Tgf-β</i>_<i>3</i> knockout mouse palates. We tested the effect of inhibiting EGF activity in vitro in the knockout palates via the addition of Tyrphostin AG 1478. We also investigated possible interactions between EGF, <i>Tgf-β</i>_<i>1</i> and <i>Msx-1</i> in <i>Tgf-β</i>_<i>3</i> null mouse palate cultures. The results show that the inhibition of EGF activity in <i>Tgf-β</i>_<i>3</i> null mouse palate cultures improves palatal shelf adhesion and fusion, with a particular effect on cell death, and restores the normal distribution pattern of <i>Msx-1</i> in the palatal mesenchyme. Inhibition of TGF-β₁ does not affect either EGF or <i>Msx-1</i> expression.