Snail family members and cell survival in physiological and pathological cleft palates.
Palate fusion is a complex process that involves the coordination of a series of cellular changes including cell death and epithelial to mesenchymal transition (EMT). Since members of the Snail family of zinc-finger regulators are involved in both triggering of the EMT and cell survival, we decided to study their putative role in palatal fusion. Furthermore, Snail genes are induced by transforming growth factor beta gene (TGF-beta) superfamily members, and TGF-beta(3) null mutant mice (TGF-beta(3)-/-) show a cleft palate phenotype. Here we show that in the wild-type mouse at the time of fusion, Snail is expressed in a few cells of the midline epithelial seam (MES), compatible with a role in triggering of the EMT in a small subpopulation of the MES. We also find an intriguing relationship between the expression of Snail family members and cell survival associated to the cleft palate condition. Indeed, Snail is expressed in the medial edge epithelial (MEE) cells in TGF-beta(3)-/-mouse embryo palates, where it is activated by the aberrant expression of its inducer, TGF-beta(1), in the underlying mesenchyme. In contrast to Snail-deficient wild-type pre-adhesion MEE cells, Snail-expressing TGF-beta(3) mutant MEE cells survive as they do their counterparts in the chick embryo. Interestingly, Slug is the Snail family member expressed in the chick MEE, providing another example of interchange of Snail and Slug expression between avian and mammalian embryos. We propose that in the absence of TGF-beta(3), TGF-beta(1) is upregulated in the mesenchyme, and that in both physiological (avian) and pathological (TGF-beta(3)-/-mammalian) cleft palates, it induces the expression of Snail genes promoting the survival of the MEE cells and permitting their subsequent differentiation into keratinized stratified epithelium.
Martínez-Alvarez
Concepción
C
Departamento de Anatomía y Embriología Humana I, Facultad de Medicina, Universidad Complutense de Madrid, 28040 Madrid, Spain.
Blanco
María J
MJ
Pérez
Raquel
R
Rabadán
M Angeles
MA
Aparicio
Marta
M
Resel
Eva
E
Martínez
Tamara
T
Nieto
M Angela
MA
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002972:Cleft Palate / Q000196:embryology / Q000662:veterinary*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004848:Epithelium / Q000196:embryology; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008817:Mice, Mutant Strains; D010159:Palate / Q000196:embryology*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000502:physiology*; D016335:Zinc Fingers / Q000502:physiology*
D004268:DNA-Binding Proteins; C000604449:Snai2 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D016212:Transforming Growth Factor beta