title: Epidermal growth factor impairs palatal shelf adhesion and fusion in the Tgf-β 3 null mutant.
abstract: The cleft palate presented by transforming growth factor-β3 (Tgf-β3) 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 (Tgf-β1) and muscle segment homeobox-1 (Msx-1) 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 Tgf-β3 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, Tgf-β1 and Msx-1 in Tgf-β3 null mouse palate cultures. The results show that the inhibition of EGF activity in Tgf-β3 null mouse palate cultures improves palatal shelf adhesion and fusion, with a particular effect on cell death, and restores the normal distribution pattern of Msx-1 in the palatal mesenchyme. Inhibition of TGF-β1 does not affect either EGF or Msx-1 expression.
authors.affiliation: Departamento de Anatomía y Embriología Humana I, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Barrio
authors.forename: Aurora
authors.initials: A
authors.lastname: Del Río
authors.forename: Jorge
authors.initials: J
authors.lastname: Murillo
authors.forename: Estela
authors.initials: E
authors.lastname: Maldonado
authors.forename: Yamila
authors.initials: Y
authors.lastname: López-Gordillo
authors.forename: Irene
authors.initials: I
authors.lastname: Paradas-Lara
authors.forename: Luzmarina
authors.initials: L
authors.lastname: Hernandes
authors.forename: Javier
authors.initials: J
authors.lastname: Catón
authors.forename: Concepción
authors.initials: C
authors.lastname: Martínez-Álvarez
mesh_terms: D000818:Animals; D002972:Cleft Palate / Q000378:metabolism* / Q000473:pathology; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D051957:MSX1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D053782:Transforming Growth Factor beta3 / Q000235:genetics / Q000378:metabolism*
chemical_list: D051957:MSX1 Transcription Factor; D016212:Transforming Growth Factor beta; D053782:Transforming Growth Factor beta3