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  • Title: Mouse models in palate development and orofacial cleft research: Understanding the crucial role and regulation of epithelial integrity in facial and palate morphogenesis.
    Author: Lan Y, Jiang R.
    Journal: Curr Top Dev Biol; 2022; 148():13-50. PubMed ID: 35461563.
    Abstract:
    Cleft lip and cleft palate are common birth defects resulting from genetic and/or environmental perturbations of facial development in utero. Facial morphogenesis commences during early embryogenesis, with cranial neural crest cells interacting with the surface ectoderm to form initially partly separate facial primordia consisting of the medial and lateral nasal prominences, and paired maxillary and mandibular processes. As these facial primordia grow around the primitive oral cavity and merge toward the ventral midline, the surface ectoderm undergoes a critical differentiation step to form an outer layer of flattened and tightly connected periderm cells with a non-stick apical surface that prevents epithelial adhesion. Formation of the upper lip and palate requires spatiotemporally regulated inter-epithelial adhesions and subsequent dissolution of the intervening epithelial seam between the maxillary and medial/lateral nasal processes and between the palatal shelves. Proper regulation of epithelial integrity plays a paramount role during human facial development, as mutations in genes encoding epithelial adhesion molecules and their regulators have been associated with syndromic and non-syndromic orofacial clefts. In this chapter, we summarize mouse genetic studies that have been instrumental in unraveling the mechanisms regulating epithelial integrity and periderm differentiation during facial and palate development. Since proper epithelial integrity also plays crucial roles in wound healing and cancer, understanding the mechanisms regulating epithelial integrity during facial development have direct implications for improvement in clinical care of craniofacial patients.
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