Lough K J, Byrd K M, Spitzer D C, Williams S E
1 The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
J Dent Res. 2017 Oct;96(11):1210-1220. doi: 10.1177/0022034517726284. Epub 2017 Aug 17.
Secondary palatogenesis occurs when the bilateral palatal shelves (PS), arising from maxillary prominences, fuse at the midline, forming the hard and soft palate. This embryonic phenomenon involves a complex array of morphogenetic events that require coordinated proliferation, apoptosis, migration, and adhesion in the PS epithelia and underlying mesenchyme. When the delicate process of craniofacial morphogenesis is disrupted, the result is orofacial clefting, including cleft lip and cleft palate (CL/P). Through human genetic and animal studies, there are now hundreds of known genetic alternations associated with orofacial clefts; so, it is not surprising that CL/P is among the most common of all birth defects. In recent years, in vitro cell-based assays, ex vivo palate cultures, and genetically engineered animal models have advanced our understanding of the developmental and cell biological pathways that contribute to palate closure. This is particularly true for the areas of PS patterning and growth as well as medial epithelial seam dissolution during palatal fusion. Here, we focus on epithelial cell-cell adhesion, a critical but understudied process in secondary palatogenesis, and provide a review of the available tools and mouse models to better understand this phenomenon.
继发腭发育过程发生于源自上颌突的双侧腭突在中线融合形成硬腭和软腭之时。这种胚胎学现象涉及一系列复杂的形态发生事件,这些事件需要腭突上皮及其下方间充质中细胞的增殖、凋亡、迁移和黏附相互协调。当颅面形态发生的精细过程受到干扰时,就会导致口面部裂隙,包括唇裂和腭裂(CL/P)。通过人类遗传学研究和动物研究,现已发现数百种与口面部裂隙相关的基因改变;因此,CL/P成为最常见的出生缺陷之一也就不足为奇了。近年来,基于细胞的体外试验、离体腭培养以及基因工程动物模型,增进了我们对有助于腭闭合的发育和细胞生物学途径的理解。在腭突的模式形成与生长以及腭融合过程中内侧上皮缝的溶解等方面尤其如此。在此,我们聚焦于上皮细胞间黏附,这是继发腭发育过程中一个关键但却研究不足的过程,并对现有工具和小鼠模型进行综述,以更好地理解这一现象。