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Updated: Aug 29, 2026
Method of Studying Palatal Fusion using Static Organ Culture
Published on: September 19, 2015
Snail family members and cell survival in physiological and pathological cleft palates
Concepción Martínez-Alvarez1, María J Blanco, Raquel Pérez
1Departamento de Anatomía y Embriología Humana I, Facultad de Medicina, Universidad Complutense de Madrid, 28040 Madrid, Spain.
Abstract:
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.
Insights
Snail gene expression in mouse embryos influences palate fusion by regulating cell survival and epithelial to mesenchymal transition (EMT). Aberrant TGF-beta signaling in mutant mice leads to Snail activation, promoting cell survival and contributing to cleft palate.
Area of Science:
- Developmental Biology
- Molecular Genetics
- Craniofacial Development
Background:
- Palate fusion is a critical developmental process involving cellular changes like cell death and epithelial to mesenchymal transition (EMT).
- Snail family zinc-finger regulators are implicated in EMT and cell survival.
- Transforming growth factor beta (TGF-beta) signaling, particularly TGF-beta(3), is crucial for normal palate development, as TGF-beta(3) null mutant mice exhibit cleft palates.
Purpose of the Study:
- To investigate the role of Snail family genes in mammalian palate fusion.
- To explore the relationship between Snail gene expression, TGF-beta signaling, and cell survival during palate development.
- To understand the molecular mechanisms underlying cleft palate formation in TGF-beta(3) deficient mice.
Main Methods:
- Analysis of Snail gene expression in wild-type and TGF-beta(3) null mutant mouse embryos during palate fusion.
- Examination of the relationship between TGF-beta(1) and TGF-beta(3) expression and Snail family member expression in the medial edge epithelium (MEE).
- Comparison of Snail expression and cell survival in mammalian and avian MEE cells.
Main Results:
- Snail is expressed in a subset of midline epithelial seam (MES) cells during wild-type mouse palate fusion, suggesting a role in EMT.
- In TGF-beta(3) null mutant mice, Snail is expressed in MEE cells, induced by aberrant TGF-beta(1) signaling in the mesenchyme.
- Snail-expressing MEE cells in mutant embryos survive, unlike their Snail-deficient wild-type counterparts, mirroring survival mechanisms seen in chick embryos where Slug is expressed.
Conclusions:
- TGF-beta(3) deficiency leads to aberrant TGF-beta(1) upregulation, inducing Snail gene expression in MEE cells.
- Snail gene activation promotes MEE cell survival in both pathological (TGF-beta(3)-/- mice) and physiological (chickens) contexts.
- This study elucidates a mechanism where Snail-mediated cell survival contributes to cleft palate formation in the absence of TGF-beta(3).
