IADR Abstract Archives
Periderm Formation Regulated by Sox2 Functions to Inhibit Oral Adhesions
Objectives: The periderm acts to prevent epithelial adhesions during embryogenesis and epithelial adhesions cause cleft palate and ankyloglossia. Several factors control periderm formation and in this study we have identified Sox2 as a new factor in the formation of the transient periderm structure.
Methods: Conditional ablation of Sox2 using the Pitx2Cre demonstrates multiple craniofacial and dental developmental anomalies. Immunohistochemistry, qPCR, molecular biology and biochemistry experiments reveal new roles for Sox2 during craniofacial development.
Results: The periderm fails to develop in the Sox2 conditional knockout (Sox2cKO) embryos leading to oral adhesions, ankyloglossia, cleft palate and tooth agenesis. The oral adhesions restrict elevation and extension of the palatal shelves, and inhibits dental epithelial invaginations. Sox2 expression is regulated by a Pitx2-Lef-1 network that controls the early expression of genes required for periderm formation and tooth development. However, Lef-1 overexpression can partially rescue dental development in the Sox2cKO embryos but not ankyloglossia and cleft palate. Lef-1 and Sox2 are expressed in different domains in the oral epithelium and they both interact with Pitx2 to regulate cleft palate, ankyloglossia and tooth development.
Conclusions: We demonstrate new molecular mechanisms for these factors in regulating different aspects of craniofacial development.
Methods: Conditional ablation of Sox2 using the Pitx2Cre demonstrates multiple craniofacial and dental developmental anomalies. Immunohistochemistry, qPCR, molecular biology and biochemistry experiments reveal new roles for Sox2 during craniofacial development.
Results: The periderm fails to develop in the Sox2 conditional knockout (Sox2cKO) embryos leading to oral adhesions, ankyloglossia, cleft palate and tooth agenesis. The oral adhesions restrict elevation and extension of the palatal shelves, and inhibits dental epithelial invaginations. Sox2 expression is regulated by a Pitx2-Lef-1 network that controls the early expression of genes required for periderm formation and tooth development. However, Lef-1 overexpression can partially rescue dental development in the Sox2cKO embryos but not ankyloglossia and cleft palate. Lef-1 and Sox2 are expressed in different domains in the oral epithelium and they both interact with Pitx2 to regulate cleft palate, ankyloglossia and tooth development.
Conclusions: We demonstrate new molecular mechanisms for these factors in regulating different aspects of craniofacial development.