Regulation of the Epithelial Adhesion Molecule CEACAM1 Is Important for Palate Formation

被引:14
作者
Mima, Junko [1 ,2 ]
Koshino, Aya [1 ]
Oka, Kyoko [3 ]
Uchida, Hitoshi [1 ]
Hieda, Yohki [4 ]
Nohara, Kanji [1 ]
Kogo, Mikihiko [2 ]
Chai, Yang [5 ]
Sakai, Takayoshi [1 ]
机构
[1] Osaka Univ, Dept Oral Facial Disorders, Grad Sch Dent, Suita, Osaka, Japan
[2] Osaka Univ, Grad Sch Dent, Dept Oral & Maxillofacial Surg 1, Suita, Osaka, Japan
[3] Fukuoka Dent Coll, Dept Oral Growth & Dev, Sect Pediat Dent, Fukuoka, Japan
[4] Osaka Dent Univ, Dept Biol, Kuzuha, Osaka, Japan
[5] Univ So Calif, Ctr Craniofacial Mol Biol, Ostow Sch Dent, Los Angeles, CA 90033 USA
基金
日本学术振兴会;
关键词
MEDIAL EDGE EPITHELIUM; FETAL MOUSE PALATE; CYTOPLASMIC DOMAIN; CLEFT-PALATE; IN-VITRO; CELLS; EXPRESSION; FATE; DEFECTS; ISOFORMS;
D O I
10.1371/journal.pone.0061653
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 (R) 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. TGF beta 3 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 TGF beta-deficient mice. These results suggest that CEACAM1 has roles in the initiation of palatal fusion via epithelial cell adhesion.
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页数:8
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