A TGF-beta-induced gene, betaig-h3, is crucial for the apoptotic disappearance of the medial edge epithelium in palate fusion.
TGF-beta3, TbetaR-I, and TGF-beta-activated Smad2 has been suggested to be a series of signaling molecules for secondary palate fusion. In this article, we show that a gene induced by TGF-beta, betaig-h3, is coincidentally expressed with TGF-beta3 in medial edge epithelial (MEE) cells undergoing apoptosis during normal palatal fusion. betaig-h3 was also highly expressed in the areas of post-weaning mammary gland cells and developing phalangeal joints in which TGF-beta3 or BMP-4-induced apoptosis occurs, respectively. Blocking of betaig-h3 expression in E12.5 embryos with antisense oligodeoxynucleotides (ODN) resulted in cleft of the secondary palate in 84% of the treated mice that were born. Moreover, the antisense ODN treatment resulted in a failure of apoptosis in the MEE between palatal shelves in physical contact in organ culture. We conclude that betaig-h3 expression in the MEE is stimulated by TGF-beta3, causes cell death, and consequently results in complete fusion of the apposed palatal shelves.
Department of Plastic and Reconstructive Surgery, Kyungpook National University, Daegu, Republic of Korea.
Kang-Young
KY
Choi
Hyun-Jung
HJ
Kim
Byung-Chae
BC
Cho
In-San
IS
Kim
Hyun-Jung
HJ
Kim
Hyun-Mo
HM
Ryoo
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D055415:Bone Morphogenetic Protein 4 / Q000502:physiology; D004622:Embryo, Mammalian; D004848:Epithelium / Q000196:embryology*; D016326:Extracellular Matrix Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D010159:Palate / Q000166:cytology / Q000196:embryology*; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D053782:Transforming Growth Factor beta3; D000099222:betaIG-H3 Protein
D055415:Bone Morphogenetic Protein 4; D016326:Extracellular Matrix Proteins; D016212:Transforming Growth Factor beta; D053782:Transforming Growth Factor beta3; D000099222:betaIG-H3 Protein; C525810:Bmp4 protein, mouse