Department of Oral-facial Disorders, Osaka University Graduate School of Dentistry, Suita, Osaka, Japan.
PLoS One. 2013 Apr 17;8(4):e61653. doi: 10.1371/journal.pone.0061653. Print 2013.
Cleft palate results from a mixture of genetic and environmental factors and occurs when the bilateral palatal shelves fail to fuse. The objective of this study was to search for new genes involved in mouse palate formation. Gene expression of murine embryonic palatal tissue was analyzed at various developmental stages before, during, and after palate fusion using GeneChip® microarrays. Ceacam1 was one of the highly up-regulated genes during palate formation, and this was confirmed by quantitative real-time PCR. Immunohistochemical staining showed that CEACAM1 was present in prefusion palatal epithelium and was degraded during fusion. To investigate the developmental role of CEACAM1, function-blocking antibody was added to embryonic mouse palate in organ culture. Palatal fusion was inhibited by this function-blocking antibody. To investigate the subsequent developmental role of CEACAM1, we characterized Ceacam1-deficient (Ceacam1(-/-)) mice. Epithelial cells persisted abnormally at the midline of the embryonic palate even on day E16.0, and palatal fusion was delayed in Ceacam1(-/-) mice. TGFβ3 expression, apoptosis, and cell proliferation in palatal epithelium were not affected in the palate of Ceacam1(-/-)mice. However, CEACAM1 expression was retained in the remaining MEE of TGFβ-deficient mice. These results suggest that CEACAM1 has roles in the initiation of palatal fusion via epithelial cell adhesion.
腭裂是由遗传和环境因素共同作用引起的，发生在双侧腭突未能融合时。本研究的目的是寻找参与小鼠腭裂形成的新基因。使用 GeneChip®微阵列分析了在腭融合前、融合期间和融合后不同发育阶段的胚胎腭组织的基因表达。在腭形成过程中，Ceacam1 是高度上调的基因之一，这通过定量实时 PCR 得到了证实。免疫组织化学染色显示 CEACAM1 存在于融合前的腭上皮中，并在融合过程中降解。为了研究 CEACAM1 的发育作用，在器官培养中将功能阻断抗体添加到胚胎小鼠腭中。这种功能阻断抗体抑制了腭融合。为了研究 CEACAM1 的后续发育作用，我们对 Ceacam1 缺陷（Ceacam1(-/-)）小鼠进行了特征描述。即使在 E16.0 天，上皮细胞仍异常地存在于胚胎腭的中线处，并且 Ceacam1(-/-)小鼠的腭融合延迟。在 Ceacam1(-/-)小鼠的腭上皮中，TGFβ3 表达、细胞凋亡和细胞增殖不受影响。然而，CEACAM1 表达在 TGFβ 缺陷型小鼠的剩余 MEE 中保留。这些结果表明，CEACAM1 通过上皮细胞黏附在腭融合的启动中起作用。
