Mouse models in palate development and orofacial cleft research: Understanding the crucial role and regulation of epithelial integrity in facial and palate morphogenesis.
Mouse models in palate development and orofacial cleft research: Understanding the crucial role and regulation of epithelial integrity in facial and palate morphogenesis.
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DOI：
10.1016/bs.ctdb.2021.12.003
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发表时间：
2022
影响因子：
--
通讯作者：
Jiang, Rulang
中科院分区：
文献类型：
--
作者：
Lan, Yu;Jiang, Rulang
唇裂和腭裂是常见的出生缺陷，是由于子宫内面部发育的遗传和/或环境扰动造成的。面部形态发生在早期胚胎发生期间开始，颅神经嵴细胞与表面外胚层相互作用，形成最初部分独立的面部原基，由内侧和外侧鼻突起以及成对的上颌和下颌突组成。当这些面部原基在原始口腔周围生长并向腹侧中线融合时，表面外胚层经历关键的分化步骤，形成扁平且紧密连接的周皮细胞外层，并具有防止上皮粘附的不粘顶端表面。上唇和上腭的形成需要时空调节的上皮间粘连，以及随后上颌骨和内侧/外侧鼻突之间以及腭架之间的介入上皮接缝的溶解。上皮完整性的适当调节在人类面部发育过程中起着至关重要的作用，因为编码上皮粘附分子及其调节因子的基因突变与综合征性和非综合征性口面裂有关。在本章中，我们总结了小鼠遗传学研究，这些研究有助于揭示面部和上颚发育过程中上皮完整性和周皮分化的调节机制。由于适当的上皮完整性在伤口愈合和癌症中也起着至关重要的作用，因此了解面部发育过程中调节上皮完整性的机制对于改善颅面患者的临床护理具有直接影响。
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 towards 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.