Division in Anatomy and Developmental Biology, Department of Oral Biology, Research Center for Orofacial Hard Tissue Regeneration, Oral Science Research Center, College of Dentistry, Yonsei University, Seodaemoon-Gu, Seoul, Korea.
Histochem Cell Biol. 2012 Apr;137(4):459-70. doi: 10.1007/s00418-012-0915-6. Epub 2012 Jan 20.
Palate development requires coordinating proper cellular and molecular events in palatogenesis, including the epithelial-mesenchymal transition (EMT), apoptosis, cell proliferation, and cell migration. Zeb1 and Zeb2 regulate epithelial cadherin (E-cadherin) and EMT during organogenesis. While microRNA 200b (miR-200b) is known to be a negative regulator of Zeb1 and Zeb2 in cancer progression, its regulatory effects on Zeb1 and Zeb2 in palatogenesis have not yet been clarified. The aim of this study is to investigate the relationship between the regulators of palatal development, specifically, miR-200b and the Zeb family. Expression of both Zeb1 and Zeb2 was detected in the mesenchyme of the mouse palate, while miR-200b was expressed in the medial edge epithelium. After contact with the palatal shelves, miR-200b was expressed in the palatal epithelial lining and epithelial island around the fusion region but not in the palatal mesenchyme. The function of miR-200b was examined by overexpression via a lentiviral vector in the palatal shelves. Ectopic expression of miR-200b resulted in suppression of the Zeb family, upregulation of E-cadherin, and changes in cell migration and palatal fusion. These results suggest that miR-200b plays crucial roles in cell migration and palatal fusion by regulating Zeb1 and Zeb2 as a noncoding RNA during palate development.
palate 发育需要协调腭发生过程中的适当细胞和分子事件,包括上皮-间充质转化 (EMT)、细胞凋亡、细胞增殖和细胞迁移。Zeb1 和 Zeb2 在器官发生过程中调节上皮钙黏蛋白 (E-cadherin) 和 EMT。虽然 microRNA 200b (miR-200b) 已知是癌症进展中 Zeb1 和 Zeb2 的负调节剂,但它对腭发生中 Zeb1 和 Zeb2 的调节作用尚未阐明。本研究旨在探讨腭发育调节剂,特别是 miR-200b 和 Zeb 家族之间的关系。在小鼠腭的间质中检测到 Zeb1 和 Zeb2 的表达,而 miR-200b 在中轴上皮中表达。与腭架接触后,miR-200b 在融合区周围的腭上皮衬里和上皮岛中表达,但不在腭间质中表达。通过慢病毒载体在腭架中过表达来检查 miR-200b 的功能。miR-200b 的异位表达导致 Zeb 家族的抑制、E-cadherin 的上调以及细胞迁移和腭融合的变化。这些结果表明,miR-200b 通过作为非编码 RNA 调节 Zeb1 和 Zeb2 在细胞迁移和腭融合中发挥关键作用。